U.S. patent application number 14/151951 was filed with the patent office on 2014-05-08 for oxygen-substituted 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals.
This patent application is currently assigned to SANOFI. The applicant listed for this patent is Christian BUNING, Georg HORSTICK, Thomas OLPP, Josef PERNERSTORFER, Sven RUF, Thorsten SADOWSKI, Bodo SCHEIPER, Herman SCHREUDER, Klaus WIRTH. Invention is credited to Christian BUNING, Georg HORSTICK, Thomas OLPP, Josef PERNERSTORFER, Sven RUF, Thorsten SADOWSKI, Bodo SCHEIPER, Herman SCHREUDER, Klaus WIRTH.
Application Number | 20140128616 14/151951 |
Document ID | / |
Family ID | 42035666 |
Filed Date | 2014-05-08 |
United States Patent
Application |
20140128616 |
Kind Code |
A1 |
RUF; Sven ; et al. |
May 8, 2014 |
OXYGEN-SUBSTITUTED 3-HETEROAROYLAMINO-PROPIONIC ACID DERIVATIVES
AND THEIR USE AS PHARMACEUTICALS
Abstract
The present invention relates to compounds of the formula I,
wherein A, D, E, G, R.sup.10, R.sup.30, R.sup.40, R.sup.50 and
R.sup.60 have the meanings indicated in the claims, which are
valuable pharmaceutical active compounds. They are inhibitors of
the protease cathepsin A, and are useful for the treatment of
diseases such as atherosclerosis, heart failure, renal diseases,
liver diseases or inflammatory diseases, for example. The invention
furthermore relates to processes for the preparation of the
compounds of the formula I, their use and pharmaceutical
compositions comprising them. ##STR00001##
Inventors: |
RUF; Sven; (Frankfurt am
Main, DE) ; PERNERSTORFER; Josef; (Frankfurt am Main,
DE) ; SADOWSKI; Thorsten; (Frankfurt am Main, DE)
; HORSTICK; Georg; (Frankfurt am Main, DE) ;
SCHREUDER; Herman; (Frankfurt am Main, DE) ; BUNING;
Christian; (Frankfurt am Main, DE) ; OLPP;
Thomas; (Frankfurt am Main, DE) ; SCHEIPER; Bodo;
(Frankfurt am Main, DE) ; WIRTH; Klaus; (Frankfurt
am Main, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RUF; Sven
PERNERSTORFER; Josef
SADOWSKI; Thorsten
HORSTICK; Georg
SCHREUDER; Herman
BUNING; Christian
OLPP; Thomas
SCHEIPER; Bodo
WIRTH; Klaus |
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main
Frankfurt am Main |
|
DE
DE
DE
DE
DE
DE
DE
DE
DE |
|
|
Assignee: |
SANOFI
Paris
FR
|
Family ID: |
42035666 |
Appl. No.: |
14/151951 |
Filed: |
January 10, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13575008 |
Oct 22, 2012 |
8664257 |
|
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PCT/EP2011/051038 |
Jan 26, 2011 |
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14151951 |
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61309119 |
Mar 1, 2010 |
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Current U.S.
Class: |
548/369.7 ;
560/38 |
Current CPC
Class: |
C07D 231/22 20130101;
A61P 11/06 20180101; A61P 37/02 20180101; A61P 19/02 20180101; A61P
37/00 20180101; A61P 3/10 20180101; A61P 9/00 20180101; A61P 7/10
20180101; C07D 403/12 20130101; A61P 25/04 20180101; A61P 25/28
20180101; C07D 401/12 20130101; A61P 25/00 20180101; C07D 231/20
20130101; C07D 413/12 20130101; A61P 9/12 20180101; C07D 401/04
20130101; A61P 13/12 20180101; C07D 417/12 20130101; A61P 11/00
20180101; C07D 405/12 20130101; A61P 7/02 20180101; A61P 29/00
20180101; A61P 7/12 20180101; C07C 229/36 20130101; A61P 9/04
20180101; A61P 9/10 20180101; A61P 13/00 20180101 |
Class at
Publication: |
548/369.7 ;
560/38 |
International
Class: |
C07D 231/22 20060101
C07D231/22; C07C 229/36 20060101 C07C229/36 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 26, 2010 |
EP |
10305080.3 |
Claims
1-14. (canceled)
15. A compound
1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid
##STR00042##
16. A compound 5-Methoxy-1-phenyl-1H-pyrazole-3-carboxylic acid
##STR00043##
17. A compound Methyl
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate
##STR00044##
18. A compound
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
##STR00045##
19. A compound Ethyl (S)-3-amino-3-(2-methyl-phenyl)-propionate
##STR00046##
Description
[0001] The present invention relates to compounds of the formula
I,
##STR00002##
wherein A, D, E, G, R.sup.10, R.sup.30, R.sup.40, R.sup.50 and
R.sup.60 have the meanings indicated below, which are valuable
pharmaceutical active compounds. They are inhibitors of the
protease cathepsin A, and are useful for the treatment of diseases
such as atherosclerosis, heart failure, renal diseases, liver
diseases or inflammatory diseases, for example. The invention
furthermore relates to processes for the preparation of the
compounds of the formula I, their use and pharmaceutical
compositions comprising them.
[0002] Cathepsin A (EC=3.4.16.5; gene symbol CTSA) is a protease
also known as lysosomal carboxypeptidase A or protective protein.
It belongs to a family of serine carboxypeptidases which contains
only two other mammalian representatives, retinoid-inducible serine
carboxypeptidase and vitellogenic carboxypeptidase-like protein.
Within the cell cathepsin A resides in lysosomes where it forms a
high molecular weight complex with beta-galactosidase and
neuraminidase. The interaction of cathepsin A with these
glycosidases is essential for their correct routing to the lysosome
and protects them from intralysosomal proteolysis. A deficiency of
cathepsin A resulting from various mutations in the ctsa gene leads
to a secondary deficiency of beta-galactosidase and neuraminidase
that is manifest as the autosomal recessive lysosomal storage
disorder galactosialidosis (cf. A. d'Azzo et al., in "The Metabolic
and Molecular Bases of Inherited Disease", vol. 2 (1995),
2835-2837). The majority of identified mutations in ctsa are
missense mutations affecting the folding or the stability of the
protein. None of them was shown to occur in the active site of the
enzyme (G. Rudenko et al., Proc. Natl. Acad. Sci. USA 95 (1998),
621-625). Accordingly, the lysosomal storage disorder can be
corrected with catalytically inactive cathepsin A mutants (N. J.
Galjart et al., J. Biol. Chem. 266 (1991), 14754-14762). The
structural function of cathepsin A is therefore separable from its
catalytic activity. This is also underscored by the observation
that in contrast to mice deficient in the ctsa gene, mice carrying
a catalytically inactivating mutation in the ctsa gene do not
develop signs of the human disease galactosialidosis (R. J. Rottier
et al., Hum. Mol. Genet. 7 (1998), 1787-1794; V. Seyrantepe et al.,
Circulation 117 (2008), 1973-1981).
[0003] Cathepsin A displays carboxypeptidase activity at acidic pH
and deamidase and esterase activities at neutral pH against various
naturally occurring bioactive peptides. In vitro studies have
indicated that cathepsin A converts angiotensin I to angiotensin
1-9 and bradykinin to bradykinin 1-8, which is the ligand for the
bradykinin B1 receptor. It hydrolyzes endothelin-1, neurokinin and
oxytocin, and deamidates substance P (cf. M. Hiraiwa, Cell. Mol.
Life. Sci. 56 (1999), 894-907). High cathepsin A activity has been
detected in urine, suggesting that it is responsible for tubular
bradykinin degradation (M. Saito et al., Int. J. Tiss. Reac. 17
(1995), 181-190). However, the enzyme can also be released from
platelets and lymphocytes and is expressed in antigen-presenting
cells where it might be involved in antigen processing (W. L. Hanna
et al., J. Immunol. 153 (1994), 4663-4672; H. Ostrowska, Thromb.
Res. 86 (1997), 393-404; M. Reich et al., Immunol. Lett. (online
Nov. 30, 2009)). Immunohistochemistry of human organs revealed
prominent expression in renal tubular cells, bronchial epithelial
cells, Leydig's cells of the testis and large neurons of the brain
(O, Sohma et al., Pediatr. Neurol. 20 (1999), 210-214). It is
upregulated during differentiation of monocytes to macrophages (N.
M. Stamatos et al., FEBS J. 272 (2005), 2545-2556). Apart from
structural and enzymatic functions, cathepsin A has been shown to
associate with neuraminidase and an alternatively spliced
beta-galactosidase to form the cell-surface laminin and elastin
receptor complex expressed on fibroblasts, smooth muscle cells,
chondroblasts, leukocytes and certain cancer cell types (A. Hinek,
Biol. Chem. 377 (1996), 471-480).
[0004] The importance of cathepsin A for the regulation of local
bradykinin levels has been demonstrated in animal models of
hypertension. Pharmacological inhibition of cathepsin A activity
increased renal bradykinin levels and prevented the development of
salt-induced hypertension (H. Ito et al., Br. J. Pharmacol. 126
(1999), 613-620). This could also be achieved by antisense
oligonucleotides suppressing the expression of cathepsin A (I.
Hajashi et al., Br. J. Pharmacol. 131 (2000), 820-826). Besides in
hypertension, beneficial effects of bradykinin have been
demonstrated in various further cardiovascular diseases and other
diseases (cf. J. Chao et al., Biol. Chem. 387 (2006), 665-75; P.
Madeddu et al., Nat. Clin. Pract. Nephrol. 3 (2007), 208-221). Key
indications of cathepsin A inhibitors therefore include
atherosclerosis, heart failure, cardiac infarction, cardiac
hypertrophy, vascular hypertrophy, left ventricular dysfunction, in
particular left ventricular dysfunction after myocardial
infarction, renal diseases such as renal fibrosis, renal failure
and kidney insufficiency; liver diseases such as liver fibrosis and
liver cirrhosis, diabetes complications such as nephropathy, as
well as organ protection of organs such as the heart and the
kidney.
[0005] As indicated above, cathepsin A inhibitors can prevent the
generation of the bradykinin B1 receptor ligand bradykinin 1-8 (M.
Saito et al., Int. J. Tiss. Reac. 17 (1995), 181-190). This offers
the opportunity to use cathepsin A inhibitors for the treatment of
pain, in particular neuropathic pain, and inflammation, as has been
shown for bradykinin B1 receptor antagonists (cf. F. Marceau et
al., Nat. Rev. Drug Discov. 3 (2004), 845-852). Cathepsin A
inhibitors can further be used as anti-platelet agents as has been
demonstrated for the cathepsin A inhibitor ebelactone B, a
propiolactone derivative, which suppresses platelet aggregation in
hypertensive animals (H. Ostrowska et al., J. Cardiovasc.
Pharmacol. 45 (2005), 348-353).
[0006] Further, like other serine proteases such as prostasin,
elastase or matriptase, cathepsin A can stimulate the
amiloride-sensitive epithelial sodium channel (ENaC) and is thereby
involved in the regulation of fluid volumes across epithelial
membranes (cf. C. Planes et al., Curr. Top. Dev. Biol. 78 (2007),
23-46). Thus, respiratory diseases can be ameliorated by the use of
cathepsin A inhibitors, such as cystic fibrosis, chronic
bronchitis, chronic obstructive pulmonary disease, asthma,
respiratory tract infections and lung carcinoma. Cathepsin A
modulation in the kidney could be used to promote diuresis and
thereby induce a hypotensive effect.
[0007] Besides for the above-mentioned compound ebelactone B, an
inhibitory effect on cathepsin A has been found for certain
dipeptidic phenylalanine derivatives which are described in JP
2005/145839. There is a need for further compounds which inhibit
cathepsin A and offer an opportunity for the treatment of the
mentioned diseases and further diseases in which cathepsin A plays
a role. The present invention satisfies this need by providing the
oxygen-substituted 3-heteroaroylamino-propionic acid derivatives of
the formula I defined below.
[0008] Certain compounds in which a 3-heteroaroylamino-propionic
acid moiety can be present, have already been described. For
example, in WO 2006/076202 amine derivatives, which modulate the
activity of steroid nuclear receptors, are described which carry on
the nitrogen atom of the amine function a heteroaroyl group and a
further group which is defined very broadly. In US 2004/0072802
broadly-defined beta-amino acid derivatives are described which
carry an acyl group on the beta-amino group and are inhibitors of
matrix metalloproteases and/or tumor necrosis factor. In WO
2009/080226 and WO 2009/080227, which relate to antagonists of the
platelet ADP receptor P2Y12 and inhibit platelet aggregation,
pyrazoloylamino-substituted carboxylic acid derivatives are
described which, however, additionally carry a carboxylic acid
derivative group on the carbon atom carrying the pyrazoloylamino
group. Other pyrazoloylamino-substituted compounds, in which the
nitrogen atom of the amino group is connected to a ring system and
which are inhibitors of the blood clotting enzymes factor Xa and/or
factor VIIa, are described in WO 2004/056815.
[0009] A subject of the present invention is a compound of the
formula I, in any of its stereoisomeric forms or a mixture of
stereoisomeric forms in any ratio, or a physiologically acceptable
salt thereof, or a physiologically acceptable solvate of any of
them,
##STR00003##
wherein A is chosen from the series consisting of C(R.sup.1) and N;
D is chosen from the series consisting of N(R.sup.2), O and S; E is
chosen from the series consisting of C(R.sup.3) and N; G is chosen
from the series consisting of R.sup.71--O--C(O)--,
R.sup.72--N(R.sup.73)--C(O)--, NC-- and tetrazol-5-yl; R.sup.1 is
chosen from the series consisting of hydrogen, halogen,
(C.sub.1-C.sub.6)-alkyl, Ar, HO--, (C.sub.1-C.sub.6)-alkyl-O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m-- and NC--; R.sup.2 is chosen
from the series consisting of (C.sub.1-C.sub.7)-alkyl,
(C.sub.3-C.sub.7)-cycloalkyl-C.sub.sH.sub.2s-- and
Ar--C.sub.sH.sub.2s--, wherein s is an integer chosen from the
series consisting of 0, 1, 2 and 3; R.sup.3 is chosen from the
series consisting of hydrogen, halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.1-C.sub.6)-alkyl-O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--
and NC--; R.sup.10 is chosen from the series consisting of
R.sup.11--O--, R.sup.12--N(R.sup.13)--C(O)--O-- and
Het.sup.2-C(O)--O--; R.sup.11 is chosen from the series consisting
of hydrogen, R.sup.14, (C.sub.3-C.sub.7)-cycloalkyl, Ar and
Het.sup.3; R.sup.12 and R.sup.13 are independently of each other
chosen from the series consisting of hydrogen, R.sup.15 and Ar;
R.sup.14 is (C.sub.1-C.sub.10)-alkyl which is optionally
substituted by one or more identical or different substituents
chosen from the series consisting of halogen, HO--, R.sup.16--O--,
oxo, (C.sub.3-C.sub.7)--cycloalkyl, Ar, Het.sup.1, Het.sup.3, NC--,
H.sub.2N--C(O)--, (C.sub.1-C.sub.4)-alkyl-NH--C(O)--,
di((C.sub.1-C.sub.4)-alkyl)N--C(O)--, Het.sup.1-C(O)--,
(C.sub.1-C.sub.4)-alkyl-C(O)--NH-- and
(C.sub.1-C.sub.4)-alkyl-S(O).sub.m--; R.sup.15 is
(C.sub.1-C.sub.6)-alkyl which is optionally substituted by one or
more identical or different substituents chosen from the series
consisting halogen, HO-- and (C.sub.1-C.sub.6)-alkyl-O--; R.sup.16
is (C.sub.1-C.sub.6)-alkyl which is optionally substituted by one
or more identical or different substituents chosen from the series
consisting of HO--, (C.sub.1-C.sub.4)-alkyl-O-- and NC--; R.sup.30
is chosen from the series consisting of R.sup.31,
(C.sub.3-C.sub.7)-cycloalkyl, R.sup.32--C.sub.uH.sub.2u-- and
Het.sup.3-C.sub.uH.sub.2u--, wherein u is an integer chosen from
the series consisting of 0, 1, 2 and 3; R.sup.31 is
(C.sub.1-C.sub.10)-alkyl which is optionally substituted by one or
more identical or different substituents chosen from the series
consisting of halogen, (C.sub.3-C.sub.7)-cycloalkyl, HO--,
(C.sub.1-C.sub.6)-alkyl-O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--
and NC--; R.sup.32 is chosen from the series consisting of phenyl
and an aromatic 5-membered or 6-membered monocyclic heterocycle
which comprises one, two or three identical or different ring
heteroatoms chosen from the series consisting of nitrogen, oxygen
and sulfur and is bonded via a ring carbon atom, wherein the phenyl
and the heterocycle all are optionally substituted by one or more
identical or different substituents chosen from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.7)-cycloalkyl, R.sup.33, HO--,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
H.sub.2N--S(O).sub.2--, (C.sub.1-C.sub.4)-alkyl-NH--S(O).sub.2--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--, H.sub.2N--,
(C.sub.1-C.sub.6)-alkyl-NH--, di((C.sub.1-C.sub.6)-alkyl)N--,
Het.sup.1, (C.sub.1-C.sub.4)-alkyl-C(O)--NH--, Ar--C(O)--NH--,
(C.sub.1-C.sub.4)-alkyl-S(O).sub.2--NH-- and NC--; R.sup.33 is
chosen from the series consisting of phenyl and an aromatic
5-membered or 6-membered monocyclic heterocycle which comprises
one, two or three identical or different ring heteroatoms chosen
from the series consisting of nitrogen, oxygen and sulfur and is
bonded via a ring carbon atom, wherein the phenyl and the
heterocycle all are optionally substituted by one or more identical
or different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl,
HO--, (C.sub.1-C.sub.6)-alkyl-O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m--, H.sub.2N--S(O).sub.2--,
(C.sub.1-C.sub.4)-alkyl-NH--S(O).sub.2--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2-- and NC--; R.sup.40 is
chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.4)-alkyl; or R.sup.30 and R.sup.40 together are
(CH.sub.2).sub.x which is optionally substituted by one or more
identical or different (C.sub.1-C.sub.4)-alkyl substituents,
wherein x is an integer chosen from the series consisting of 2, 3,
4 and 5; R.sup.50 is chosen from the series consisting of hydrogen,
(C.sub.1-C.sub.6)-alkyl, HO-- and (C.sub.1-C.sub.6)-alkyl-O--;
R.sup.60 is chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.6)-alkyl; or R.sup.50 and R.sup.60 together are
(CH.sub.2).sub.y which is optionally substituted by one or more
identical or different (C.sub.1-C.sub.4)-alkyl substituents,
wherein y is an integer chosen from the series consisting of 2, 3,
4 and 5; R.sup.71 is chosen from the series consisting of hydrogen
and (C.sub.1-C.sub.8)-alkyl which is optionally substituted by one
or more identical or different substituents chosen from the series
consisting (C.sub.1-C.sub.6)-alkyl-O-- and
(C.sub.1-C.sub.6)-alkyl-C(O)--O--; R.sup.72 is chosen from the
series consisting of hydrogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.6)-cycloalkyl,
--CH.sub.2--(CH.sub.2).sub.b--(C.sub.3-C.sub.6)-cycloalkyl,
Het.sup.4 and --(CH.sub.2).sub.b-Het.sup.4, where alkyl or
cycloalkyl is optionally substituted by one or more identical or
different substituents chosen from the series consisting of
halogen, HO--, HOOC--, (C.sub.1-C.sub.6)-alkyl-O-- and
(C.sub.1-C.sub.6)-alkyl-C(O)--O--, NC--,
N((C.sub.1-C.sub.4)-alkyl).sub.2 and b is 0, 1 or 2; R.sup.73 is
chosen from the series consisting of hydrogen,
(C.sub.1-C.sub.6)-alkyl; or R.sup.72 and R.sup.73 together with the
nitrogen atom to which they are bonded form a saturated 4-membered
to 7-membered monocyclic heterocycle, which contain optionally one
further ring heteroatom chosen from the series consisting of
nitrogen, oxygen and sulfur, which is optionally substituted by one
or more identical or different substituents chosen from the series
consisting of halogen, (C.sub.1-C.sub.4)-alkyl, HO-- and
(C.sub.1-C.sub.4)-alkyl-O--; Ar, independently of each other group
Ar, is chosen from the series consisting of phenyl and an aromatic
5-membered or 6-membered monocyclic heterocycle which comprises
one, two or three identical or different ring heteroatoms chosen
from the series consisting of nitrogen, oxygen and sulfur and is
bonded via a ring carbon atom, wherein the phenyl and the
heterocycle all are optionally substituted by one or more identical
or different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O--,
--O--CH.sub.2--O--, --O--CF.sub.2--O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m--, H.sub.2N--S(O).sub.2-- and
NC--; Het.sup.1, independently of each other group Het.sup.1, is a
saturated or unsaturated 4-membered to 8-membered monocyclic
heterocycle which comprises a ring nitrogen atom via which
Het.sup.1 is bonded and optionally one or two identical or
different further ring heteroatoms chosen from the series
consisting of nitrogen, oxygen and sulfur, which is optionally
substituted by one or more identical or different substituents
chosen from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl, HO--, (C.sub.1-C.sub.4)-alkyl-O--, oxo and
NC--; Het.sup.2 is a saturated 4-membered to 7-membered monocyclic
heterocycle which comprises a ring nitrogen atom via which
Het.sup.2 is bonded and optionally one further ring heteroatom
chosen from the series consisting of nitrogen, oxygen and sulfur,
which is optionally substituted by one or more identical or
different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, HO-- and
(C.sub.1-C.sub.4)-alkyl-O--; Het.sup.3, independently of each other
group Het.sup.3, is a saturated 4-membered to 7-membered monocyclic
heterocycle which comprises one or two identical or different ring
heteroatoms chosen from the series consisting of nitrogen, oxygen
and sulfur and is bonded via a ring carbon atom, which is
optionally substituted by one or more identical or different
substituents chosen from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl and oxo; Het.sup.4, independently of each
other group Het.sup.4, is a saturated or unsaturated 4-membered to
8-membered monocyclic heterocycle which comprises one to four ring
heteroatoms chosen from the series consisting of nitrogen, oxygen
and sulfur which is optionally substituted by one or more identical
or different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, HO--,
(C.sub.1-C.sub.4)-alkyl-O--, oxo and NC--; m, independently of each
other number m, is an integer chosen from the series consisting of
0, 1 and 2; wherein all cycloalkyl groups, independently of each
other, are optionally substituted by one or more identical or
different substituents chosen from the series consisting of
fluorine and (C.sub.1-C.sub.4)-alkyl; wherein all alkyl,
C.sub.sH.sub.2s, C.sub.uH.sub.2u, (CH.sub.2).sub.x and
(CH.sub.2).sub.y groups, independently of each other, and
independently of any other substituents, are optionally substituted
by one or more fluorine substituents.
[0010] If structural elements such as groups, substituents or
numbers, for example, can occur several times in the compounds of
the formula I, they are all independent of each other and can in
each case have any of the indicated meanings, and they can in each
case be identical to or different from any other such element. In a
dialkylamino group, for example, the alkyl groups can be identical
or different.
[0011] Alkyl groups, i.e. saturated hydrocarbon residues, can be
linear (straight-chain) or branched. This also applies if these
groups are substituted or are part of another group, for example an
alkyl-O-- group (alkyloxy group, alkoxy group) or an HO-substituted
alkyl group (hydroxyalkyl group). Depending on the respective
definition, the number of carbon atoms in an alkyl group can be 1,
2, 3, 4, 5, 6, 7, 8, 9 or 10, or 1, 2, 3, 4, 5, 6, 7 or 8, or 1, 2,
3, 4, 5 or 6, or 1, 2, 3 or 4, or 1, 2 or 3, or 1 or 2, or 1, for
example. In one embodiment of the invention, a
(C.sub.1-C.sub.10)-alkyl group present in the compounds of the
formula I is a (C.sub.1-C.sub.8)-alkyl group, in another embodiment
a (C.sub.1-C.sub.6)-alkyl group, in another embodiment a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.3)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment a
(C.sub.2-C.sub.3)-alkyl group, in another embodiment a methyl
group. In one embodiment of the invention, a
(C.sub.1-C.sub.8)-alkyl group present in any position of the
compounds of the formula I is a (C.sub.1-C.sub.6)-alkyl group, in
another embodiment a (C.sub.1-C.sub.4)-alkyl group, in another
embodiment a (C.sub.1-C.sub.3)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment a
(C.sub.2-C.sub.3)-alkyl group, in another embodiment a methyl
group, where any (C.sub.1-C.sub.8)-alkyl group present in the
compounds of the formula I can independently of each other
(C.sub.1-C.sub.8)-alkyl group be a group of any of these
embodiments. In one embodiment of the invention, a
(C.sub.1-C.sub.6)-alkyl group present in any position of the
compounds of the formula I is a (C.sub.1-C.sub.4)-alkyl group, in
another embodiment a (C.sub.1-C.sub.3)-alkyl group, in another
embodiment a (C.sub.1-C.sub.2)-alkyl group, in another embodiment a
(C.sub.2-C.sub.3)-alkyl group, in another embodiment a methyl
group, where any (C.sub.1-C.sub.6)-alkyl group present in the
compounds of the formula I can independently of each other
(C.sub.1-C.sub.6)-alkyl group be a group of any of these
embodiments. In one embodiment of the invention, a
(C.sub.1-C.sub.4)-alkyl group present in any position of the
compounds of the formula I is a (C.sub.1-C.sub.3)-alkyl group, in
another embodiment a (C.sub.1-C.sub.2)-alkyl group, in another
embodiment a (C.sub.2-C.sub.3)-alkyl group, in another embodiment a
methyl group, where any (C.sub.1-C.sub.4)-alkyl group present in
the compounds of the formula I can independently of each other
(C.sub.1-C.sub.4)-alkyl group be a group of any of these
embodiments. Examples of alkyl groups are methyl, ethyl, propyl
groups including propyl (i.e. n-propyl) and isopropyl, butyl groups
including butyl (i.e. n-butyl), sec-butyl, isobutyl and tert-butyl,
pentyl groups including pentyl (i.e. n-pentyl), 1-methylbutyl,
isopentyl, neopentyl and tert-pentyl, hexyl groups including hexyl
(i.e. n-hexyl), 3,3-dimethylbutyl and isohexyl, heptyl groups
including heptyl (i.e. n-heptyl), octyl groups including octyl
(i.e. n-octyl), nonyl groups including nonyl (i.e. n-nonyl), and
decyl groups including decyl (i.e. n-decyl). Examples of alkyl-O--
groups are methoxy, ethoxy, propoxy (i.e. n-propoxy), isopropoxy,
butoxy (i.e. n-butoxy), isobutoxy, tert-butoxy, pentoxy (i.e.
n-pentoxy). Examples of alkyl-S(O).sub.m-- are
methylsulfanyl-(CH.sub.3--S--), methanesulfinyl-(CH.sub.3--S(O)--),
methanesulfonyl (CH.sub.3--S(O).sub.2--),
ethylsulfanyl-(CH.sub.3--CH.sub.2--S--),
ethanesulfinyl-(CH.sub.3--CH.sub.2--S(O)--), ethanesulfonyl
(CH.sub.3--CH.sub.2--S(O).sub.2--),
1-methylethylsulfanyl-((CH.sub.3).sub.2CH--S--),
1-methylethanesulfinyl-((CH.sub.3).sub.2CH--S(O)--),
1-methylethanesulfonyl ((CH.sub.3).sub.2CH--S(O).sub.2--). In one
embodiment of the invention the number m is chosen from 0 and 2,
wherein all numbers m are independent of each other and can be
identical or different. In another embodiment the number m in any
of its occurrences is, independently of its meaning in other
occurrences, 0. In another embodiment the number m in any of its
occurrences is, independently of its meaning in other occurrences,
2.
[0012] A substituted alkyl group can be substituted in any
positions, provided that the respective compound is sufficiently
stable and is suitable as a pharmaceutical active compound. The
prerequisite that a specific group and a compound of the formula I
are sufficiently stable and suitable as a pharmaceutical active
compound, applies in general with respect to the definitions of all
groups in the compounds of the formula I. In one embodiment of the
invention, an individual carbon atom in any alkyl group in the
compounds of the formula I, as well as in other groups such as
cycloalkyl groups and heterocyclic groups, for example,
independently of any other carbon atom does not carry more than one
substituent which is bonded via an oxygen atom, nitrogen atom or
sulfur atom, such as HO--, (C.sub.1-C.sub.4)-alkyl-O-- or
(C.sub.1-C.sub.4)-alkyl-S(O).sub.m-substituents, for example. An
alkyl group which is optionally substituted by one or more fluorine
substituents can be unsubstituted, i.e. not carry fluorine
substituents, or substituted, for example by one, two, three, four,
five, six, seven, eight, nine, ten or eleven fluorine substituents,
or by one, two, three, four, five, six or seven fluorine
substituents, or by one, two, three, four or five fluorine
substituents, or by one, two or three fluorine substituents, which
can be located in any positions. For example, in a
fluoro-substituted alkyl group one or more methyl groups can carry
three fluorine substituents each and be present as trifluoromethyl
groups, and/or one or more methylene groups (CH.sub.2) can carry
two fluorine substituents each and be present as difluoromethylene
groups. The explanations with respect to the substitution of a
group by fluorine also apply if the group additionally carries
other substituents and/or is part of another group, for example of
an alkyl-O-- group. Examples of fluoro-substituted alkyl groups are
trifluoromethyl, 2-fluoroethyl, 1-fluoroethyl, 1,1-difluoroethyl,
2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl,
2,2,3,3,3-pentafluoropropyl, 4,4,4-trifluorobutyl and
heptafluoroisopropyl. Examples of fluoro-substituted alkyl-O--
groups are trifluoromethoxy, 2,2,2-trifluoroethoxy,
pentafluoroethoxy and 3,3,3-trifluoropropoxy. Examples of
fluoro-substituted alkyl-S(O).sub.m-- groups are
trifluoromethylsulfanyl-(CF.sub.3--S--),
trifluoromethanesulfinyl-(CF.sub.3--S(O)--) and
trifluoromethanesulfonyl (CF.sub.3--S(O).sub.2--).
[0013] The above explanations with respect to alkyl groups apply
correspondingly to alkanediyl groups (divalent alkyl groups)
including the divalent groups C.sub.sH.sub.2s, C.sub.uH.sub.2u,
(CH.sub.2).sub.x and (CH.sub.2).sub.y. Also the alkyl part of a
substituted alkyl group may be regarded as an alkanediyl group.
Thus, alkanediyl groups can also be linear or branched, the bonds
to the adjacent groups can be located in any positions and can
start from the same carbon atom or from different carbon atoms, and
they can be substituted by fluorine substituents. Examples of
alkanediyl groups including the groups C.sub.sH.sub.2s and
C.sub.uH.sub.2u and, as far they constitute polymethylene chains,
the groups (CH.sub.2).sub.x are --CH.sub.2--,
--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--,
--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--,
--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--,
--CH(CH.sub.3)--, --C(CH.sub.3).sub.2--,
--CH(CH.sub.3)--CH.sub.2--, --CH.sub.2--CH(CH.sub.3)--,
--C(CH.sub.3).sub.2--CH.sub.2--, --CH.sub.2--C(CH.sub.3).sub.2--.
Examples of fluoro-substituted alkanediyl groups, which can contain
one, two, three, four, five or six fluorine substituents, or one,
two, three or four fluorine substituents, or one or two fluorine
substituents, for example, are --CHF--, --CF.sub.2--
--CF.sub.2--CH.sub.2--, --CH.sub.2--CF.sub.2--,
--CF.sub.2--CF.sub.2--, --CF(CH.sub.3)--, --C(CF.sub.3).sub.2--,
--C(CH.sub.3).sub.2--CF.sub.2--,
--CF.sub.2--C(CH.sub.3).sub.2--.
[0014] The number of ring carbon atoms in a
(C.sub.3-C.sub.7)-cycloalkyl group can be 3, 4, 5, 6 or 7. Examples
of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl
and cycloheptyl. As regards the optional substitution of cycloalkyl
groups by one or more (C.sub.1-C.sub.4)-alkyl substituents, they be
unsubstituted, i.e. not carry alkyl substituents, or substituted,
for example by one, two, three or four, or by one or two, identical
or different (C.sub.1-C.sub.4)-alkyl substituents, for example by
methyl groups, which substituents can be located in any positions.
Examples of such alkyl-substituted cycloalkyl groups are
1-methylcyclopropyl, 2,2-dimethylcyclopropyl, 1-methylcyclopentyl,
2,3-dimethylcyclopentyl, 1-methylcyclohexyl, 4-methylcyclohexyl,
4-isopropylcyclohexyl, 4-tert-butylcyclohexyl and
3,3,5,5-tetramethylcyclohexyl. As regards the optional substitution
of cycloalkyl groups by one or more fluorine substituents, they can
be unsubstituted, i.e. not carry fluorine substituents, or
substituted, for example by one, two, three, four, five, six,
seven, eight, nine, ten or eleven fluorine substituents, or by one,
two, three, four, five or six fluorine substituents, or by one,
two, three or four fluorine substituents, or by one or two fluorine
substituents. The fluorine substituents can be located in any
positions of the cycloalkyl group and can also be located in an
alkyl substituent on the cycloalkyl group. Examples of
fluoro-substituted cycloalkyl groups are 1-fluorocyclopropyl,
2,2-difluorocyclopropyl, 3,3-difluorocyclobutyl,
1-fluorocyclohexyl, 4,4-difluorocyclohexyl and
3,3,4,4,5,5-hexafluorocyclohexyl. Cycloalkyl groups can also be
substituted simultaneously by fluorine and alkyl. Examples of
(C.sub.3-C.sub.7)-cycloalkyl-substituted alkyl groups, which can
represent R.sup.11 or R.sup.30, for example, are
cyclopropylmethyl-, cyclobutylmethyl-, cyclopentylmethyl-,
cyclohexylmethyl-, cycloheptylmethyl-, 1-cyclopropylethyl-,
2-cyclopropylethyl-, 1-cyclobutylethyl-, 2-cyclobutylethyl-,
1-cyclopentylethyl-, 2-cyclopentylethyl-, 1-cyclohexylethyl-,
2-cyclohexylethyl-, 1-cycloheptylethyl-, 2-cycloheptylethyl-. The
explanations with respect cycloalkyl groups apply correspondingly
to divalent cycloalkyl groups (cycloalkanediyl groups), which can
occur in case the two groups R.sup.30 and R.sup.40 together are
(CH.sub.2).sub.x or the two groups R.sup.50 and R.sup.60 together
are (CH.sub.2).sub.y. Also the cycloalkyl part of a substituted
cycloalkyl group may be regarded as a cycloalkanediyl group. Thus,
for example, the bonds through which a cycloalkanediyl group is
connected to the adjacent groups, can be located in any positions
and can start from the same ring carbon atom, as in the case of the
cycloalkanediyl group which is present if R.sup.30 and R.sup.40
together are (CH.sub.2).sub.x or the two groups R.sup.50 and
R.sup.60 together are (CH.sub.2).sub.y, or from different ring
carbon atoms.
[0015] In substituted phenyl groups the substituents can be located
in any positions. In the case a the divalent substituents
--O--CH.sub.2--O-- (methylenedioxy) and
--O--CF.sub.2--O-(difluoromethylenedioxy) which can be present on
phenyl groups and aromatic heterocycles, the two oxygen atoms are
bonded to adjacent ring carbon atoms of the phenyl group or the
aromatic heterocycle and replace two hydrogen atoms of the parent
system. In monosubstituted phenyl groups, the substituent can be
located in the 2-position, the 3-position or the 4-position. In
disubstituted phenyl groups, the substituents can be located in
2,3-position, 2,4-position, 2,5-position, 2,6-position,
3,4-position or 3,5-position. In trisubstituted phenyl groups, the
substituents can be located in 2,3,4-position, 2,3,5-position,
2,3,6-position, 2,4,5-position, 2,4,6-position or 3,4,5-position.
If a phenyl group carries four substituents, some of which can be
fluorine atoms, for example, the substituents can be located in
2,3,4,5-position, 2,3,4,6-position or 2,3,5,6-position. If a
polysubstituted phenyl group carries different substituents, each
substituent can be located in any suitable position, and the
present invention comprises all positional isomers. The number of
substituents in an optionally substituted phenyl group can be one,
two, three, four or five. In one embodiment of the invention, an
optionally substituted phenyl group, independently of any other
optionally substituted phenyl group in a compound of the formula I,
carries one, two, three or four, in another embodiment one, two or
three, in another embodiment one or two, in another embodiment one,
identical or different substituents, and in another embodiment it
is unsubstituted.
[0016] Likewise, in substituted heterocyclic groups, including
aromatic 5-membered and 6-membered monocyclic heterocycles which
can represent R.sup.32, R.sup.33 and Ar, saturated and unsaturated
4-membered to 8-membered monocyclic heterocycles which can
represent Het.sup.1, and saturated 4-membered to 7-membered
monocyclic heterocycles which can represent Het.sup.2 and
Het.sup.3, the substituents can be located in any positions and can
be present on ring carbon atoms and/or on suitable ring nitrogen
atoms. The present invention comprises all positional isomers. The
number of substituents which can be present on substituted
heterocycles in the compounds of the formula I, depends on the ring
size, the number and type of the ring heteroatoms and the degree of
unsaturation. In one embodiment of the invention, the number of
identical or different substituents on any of the heterocyclic
groups in the compounds of the formula I, independently of the
number of substituents in any other occurrence of this group and
the number of substituents in any other heterocyclic group in the
compounds of the formula I, is one, two, three, four or five, in
another embodiment one, two, three or four, in another embodiment
one, two or three, in another embodiment one or two, in another
embodiment one. Ring nitrogen atoms which optionally carry a
substituent, include ring nitrogen atoms in saturated heterocyclic
rings other than those via which such a ring is bonded, and the
ring nitrogen atom in 5-membered aromatic heterocycles such as
pyrrole, imidazole or triazole, which in the parent heterocycle
carry a hydrogen atom. In one embodiment of the invention, the
substituents on any such ring nitrogen atoms in heterocyclic groups
are chosen from those of the substituents specified in the
definition of the respective group which are bonded via a carbon
atom, for example from the series consisting of
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl and R.sup.33,
in another embodiment from the series consisting of
(C.sub.1-C.sub.6)-alkyl and (C.sub.3-C.sub.7)-cycloalkyl, in the
case of the aromatic heterocycle which can represent R.sup.32, from
the series consisting of (C.sub.1-C.sub.6)-alkyl and
(C.sub.3-C.sub.7)-cycloalkyl in the case of the aromatic
heterocycle which can represent R.sup.33, and are
(C.sub.1-C.sub.6)-alkyl in the case of the aromatic heterocycle
which can represent Ar and (C.sub.1-C.sub.4)-alkyl in the case of
Het.sup.1, Het.sup.2 and Het.sup.3. Generally, besides optionally
carrying the substituents indicated in the definition of the
respective group, suitable ring nitrogen atoms in heterocyclic
groups in the compounds of the formula I, in particular aromatic
heterocyclic groups such as the heterocyclic groups which can
represent R.sup.32, R.sup.33 and Ar, for example the ring nitrogen
atom in a pyridinyl group, can also carry an oxido substituent
--O-- and be present as an N-oxide.
[0017] The ring heteroatoms specified in the definitions of
heterocyclic groups in the compounds of the formula I, including
the aromatic 5-membered and 6-membered monocyclic heterocycles
which can represent R.sup.32, R.sup.33 and Ar and the heterocycles
which represent Het.sup.1, Het.sup.2, Het.sup.3 and Het.sup.4 can
generally be present in any combination and located in any suitable
ring positions, provided that the resulting group and the compound
of the formula I are sufficiently stable and suitable as a
pharmaceutical active compound, as mentioned above. In one
embodiment of the invention, two oxygen atoms in any heterocyclic
ring in the compounds of the formula I cannot be present in
adjacent ring positions. In another embodiment, two ring
heteroatoms in any non-aromatic heterocyclic ring in the compounds
of the formula I cannot be present in adjacent ring positions. In
another embodiment, two ring heteroatoms chosen from the series
consisting of N atoms which carry a hydrogen atom or a substituent
and are bonded to the adjacent ring atoms by single bonds, O atoms
and S atoms in a non-aromatic heterocycle cannot be present in
adjacent ring positions. In an aromatic heterocycle the choice of
ring heteroatoms and their positions is limited by the prerequisite
that the ring is aromatic, i.e., it comprises a cyclic system of
six delocalized pi electrons. Thus, for example, in an aromatic
monocyclic 6-membered heterocycle only nitrogen atoms can occur as
ring heteroatoms, and in an aromatic monocyclic 5-membered
heterocycle only one ring heteroatom chosen from the series
consisting of O atoms, S atoms and N atoms carrying a hydrogen atom
or a substituent, can be present. An unsaturated heterocycle which
can represent Het.sup.1, can be aromatic, for example in the case
of a pyrrolyl, imidazolyl or triazolyl group which is bonded via a
ring nitrogen atom and can represent Het.sup.1, or non-aromatic and
comprise one or two double bonds within the ring which can be
present in any positions. In one embodiment, a 4-membered
heterocycle representing Het.sup.1 cannot be unsaturated. A
heterocyclic group can be bonded via any ring carbon atom or via
any suitable ring nitrogen atom, respectively, as indicated in the
definition of the respective group. The group Het.sup.1 can be
4-membered, 5-membered, 6-membered or 7-membered or 8-membered. The
groups Het.sup.2 and Het.sup.3 can be 4-membered, 5-membered,
6-membered or 7-membered.
[0018] Examples of aromatic heterocycles, from any one or more of
which the aromatic 5-membered and 6-membered monocyclic
heterocycles which can represent R.sup.32, R.sup.33 and Ar and, as
far as applicable, the group Het.sup.1 are chosen in one embodiment
of the invention, are pyrrole, furan, thiophene, imidazole,
pyrazole, oxazole ([1,3]oxazole), isoxazole ([1,2]oxazole),
thiazole ([1,3]thiazole), isothiazole ([1,2]thiazole),
[1,2,3]triazole, [1,2,4]triazole, [1,3,4]oxadiazole, pyridine,
pyridazine, pyrimidine and pyrazine, which can all be bonded via
any ring carbon atom or via any suitable ring nitrogen atom, and
which all are optionally substituted as indicated with respect to
the compounds of formula I in general or in any embodiment
specified above or below. Examples of specific residues of aromatic
heterocycles, from any one or more of which the aromatic,
5-membered or 6-membered monocyclic heterocyclic residue which can
represent R.sup.32, R.sup.33 or Ar and, as far as applicable, the
group Het.sup.1, are chosen in one embodiment of the invention, are
pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, furan-2-yl, furan-3-yl,
thiophen-2-yl (2-thienyl), thiophen-3-yl (3-thienyl),
imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl,
pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl,
oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl,
isoxazol-4-yl, isoxazol-5-yl, thiazol-2-yl, thiazol-4-yl,
thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl,
[1,2,3]triazol-1-yl, [1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl,
[1,2,4]triazol-1-yl, [1,2,4]triazol-3-yl, [1,2,4]triazol-4-yl,
[1,3,4]oxadiazol-2-yl, pyridin-2-yl (2-pyridyl), pyridin-3-yl
(3-pyridyl), pyridin-4-yl (4-pyridyl), pyridazin-3-yl,
pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, and pyrazin-2-yl,
which all are optionally substituted as indicated with respect to
the compounds of formula I in general or in any embodiment
specified above or below.
[0019] Examples of saturated heterocycles and non-aromatic
unsaturated heterocycles, from any one or more of which the groups
Het.sup.1, Het.sup.2, Het.sup.3 and Het.sup.4 are independently of
each other chosen in one embodiment of the invention, as far as
applicable with regard to the ring size and the degree of
saturation, are azetidine, oxetane, thietane, pyrrolidine,
2,5-dihydro-1H-pyrrole, tetrahydrofuran, tetrahydrothiophene,
pyrazolidine, imidazolidine, 4,5-dihydro-1H-imidazole,
[1,3]dioxolane, oxazolidine, thiazolidine, piperidine,
1,2,3,6-tetrahydropyridine, tetrahydropyran, tetrahydrothiopyran,
piperazine, [1,3]dioxane, [1,4]dioxane, morpholine, thiomorpholine,
azepane, oxepane, thiepane, [1,3]diazepane, [1,4]diazepane,
[1,4]oxazepane, [1,4]thiazepane and azocane, which all are
optionally substituted as indicated with respect to the compounds
of formula I in general or in any embodiment specified above or
below. Examples of specific residues of saturated and non-aromatic
unsaturated heterocycles, from any one or more of which the groups
Het.sup.1, Het.sup.2, Het.sup.3 and Het.sup.4 are independently of
each other chosen in one embodiment of the invention, as far as
applicable with regard to the ring size, the degree of saturation
and the kind of the atom via which the residue is bonded are
azetidin-1-yl, oxetan-3-yl, thietan-3-yl, pyrrolidin-1-yl,
pyrrolidin-2-yl, pyrrolidin-3-yl, 2,5-dihydro-1H-pyrrol-1-yl,
tetrahydrofuran-2-yl, tetrahydrofuran-3-yl,
tetrahydrothiophen-2-yl, tetrahydrothiophen-3-yl, pyrazolidin-1-yl,
pyrazolidin-4-yl, imidazolidin-1-yl, imidazolidin-2-yl,
imidazolidin-4-yl, 4,5-dihydro-1H-imidazol-2-yl, 1,3-dioxolan-2-yl,
1,3-dioxolan-4-yl, oxazolidin-2-yl, oxazolidin-3-yl,
oxazolidin-4-yl, oxazolidin-5-yl, thiazolidin-2-yl,
thiazolidin-3-yl, thiazolidin-4-yl, thiazolidin-5-yl,
piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl,
1,2,3,6-tetrahydropyridin-1-yl, tetrahydropyran-2-yl,
tetrahydropyran-3-yl, tetrahydropyran-4-yl,
tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl,
tetrahydrothiopyran-4-yl, piperazin-1-yl, piperazin-2-yl,
[1,3]dioxan-2-yl, [1,3]dioxan-4-yl, [1,3]dioxan-5-yl,
[1,4]dioxan-2-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl,
thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl,
azepan-1-yl, azepan-2-yl, azepan-3-yl, azepan-4-yl, oxepan-2-yl,
oxepan-3-yl, oxepan-4-yl, [1,3]diazepan-1-yl, [1,4]diazepan-1-yl,
[1,4]oxazepan-1-yl and [1,4]thiazepan-1-yl, which all are
optionally substituted as indicated with respect to the compounds
of formula I in general or in any embodiment specified above or
below.
[0020] Halogen is fluorine, chlorine, bromine or iodine. In one
embodiment of the invention, halogen in any occurrence in the
compounds of the formula I, independently of all other occurrences,
is fluorine, chlorine or bromine, in another embodiment fluorine or
chlorine, in another embodiment fluorine.
[0021] An oxo substituent, i.e. an oxygen atom which is bonded via
a double bond, when bonded to a carbon atom, replaces two hydrogen
atoms on the carbon atom of the parent system to which it is
bonded. Thus, if a CH.sub.2 group is substituted by oxo, it becomes
a carbonyl group (C(O), C.dbd.O). An oxo substituent cannot be
present on a carbon atom in an aromatic ring. Besides on carbon
atoms, oxo substituents can also be present on a ring sulfur atom
in the group Het.sup.1, in particular if the group Het.sup.1 is
saturated, and in the group Het.sup.3, to give the ring member S(O)
(S.dbd.O, i.e. a sulfoxide group), if one oxo substituent is
present on the sulfur atom, or the ring member S(O).sub.2
(S(.dbd.O).sub.2, i.e. a sulfone group), if two oxo substituents
are present on the sulfur atom. As examples of heterocycles which
can represent Het.sup.1 and Het.sup.3 and which carry oxo
substituent a ring sulfur atom, 1,1-dioxo-tetrahydrothiophene,
1-oxo-thiomorpholine and 1,1-dioxo-thiomorpholine may be mentioned,
which all are optionally substituted by further substituents such
as (C.sub.1-C.sub.4)-alkyl substituents as indicated with respect
to the compounds of formula I in general or in any embodiment
specified above or below.
[0022] The present invention comprises all stereoisomeric forms of
the compounds of the formula I, for example all enantiomers and
diastereomers including cis/trans isomers. The invention likewise
comprises mixtures of two or more stereoisomeric forms, for example
mixtures of enantiomers and/or diastereomers including cis/trans
isomers, in all ratios. Asymmetric centers contained in the
compounds of the formula I, for example in unsubstituted or
substituted alkyl groups, can all independently of each other have
the S configuration or the R configuration. The invention relates
to enantiomers, both the levorotatory and the dextrorotatory
antipode, in enantiomerically pure form and essentially
enantiomerically pure form, for example with a molar ratio of the
two enantiomers of 99:1 or greater, and in the form of racemates
and in the form of mixtures of the two enantiomers in all ratios.
The invention likewise relates to diastereomers in the form of pure
and essentially pure diastereomers and in the form of mixtures of
two or more diastereomers in all ratios. The invention also
comprises all cis/trans isomers of the compounds of the formula I
in pure form and essentially pure form, for example with a molar
ratio of the cis/trans isomers of 99:1 or greater, and in the form
of mixtures of the cis isomer and the trans isomer in all ratios.
Cis/trans isomerism can occur in substituted rings. The preparation
of individual stereoisomers, if desired, can be carried out by
resolution of a mixture according to customary methods, for
example, by chromatography or crystallization, or by use of
stereochemically uniform starting compounds in the synthesis or by
stereoselective reactions. Optionally, before a separation of
stereoisomers a derivatization can be carried out. The separation
of a mixture of stereoisomers can be carried out at the stage of
the compound of the formula I or at the stage of an intermediate in
the course of the synthesis. The invention also comprises all
tautomeric forms of the compounds of the formula I.
[0023] Physiologically acceptable salts, including pharmaceutically
utilizable salts, of the compounds of the formula I generally
comprise a nontoxic salt component. They can contain inorganic or
organic salt components. Such salts can be formed, for example,
from compounds of the formula I which contain an acidic group, for
example a carboxylic acid group (hydroxycarbonyl group,
HO--C(O)--), and nontoxic inorganic or organic bases. Suitable
bases are, for example, alkali metal compounds or alkaline earth
metal compounds, such as sodium hydroxide, potassium hydroxide,
sodium carbonate or sodium hydrogencarbonate, or ammonia, organic
amino compounds and quaternary ammonium hydroxides. Reactions of
compounds of the formula I with bases for the preparation of the
salts are in general carried out according to customary procedures
in a solvent or diluent. Examples of salts of acidic groups thus
are sodium, potassium, magnesium or calcium salts or ammonium salts
which can also carry one or more organic groups on the nitrogen
atom. Compounds of the formula I which contain a basic, i.e.
protonatable, group, for example an amino group or a basic
heterocycle, can be present in the form of their acid addition
salts with physiologically acceptable acids, for example as salt
with hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric
acid, acetic acid, benzoic acid, methanesulfonic acid,
p-toluenesulfonic acid, which in general can be prepared from the
compounds of the formula I by reaction with an acid in a solvent or
diluent according to customary procedures. If the compounds of the
formula I simultaneously contain an acidic and a basic group in the
molecule, the invention also includes internal salts (betaines,
zwitterions) in addition to the salt forms mentioned. The present
invention also comprises all salts of the compounds of the formula
I which, because of low physiological tolerability, are not
directly suitable for use as a pharmaceutical, but are suitable as
intermediates for chemical reactions or for the preparation of
physiologically acceptable salts, for example by means of anion
exchange or cation exchange. The present invention also comprises
all solvates of the compounds of the formula I and their salts,
including physiologically acceptable solvates, such as hydrates,
i.e. adducts with water, and adducts with alcohols like
(C.sub.1-C.sub.4)-alkanols, as well as active metabolites of
compounds of the formula I and prodrugs of the compounds of the
formula I, i.e. compounds which in vitro may not necessarily
exhibit pharmacological activity but which in vivo are converted
into pharmacologically active compounds of the formula I, for
example compounds which are converted by metabolic hydrolysis into
a compound of the formula I, such as compounds in which a
carboxylic acid group is present in esterified form or in the form
of an amide.
[0024] In one embodiment of the invention, the group A is
C(R.sup.1), in another embodiment A is N. In one embodiment of the
invention, the group D is chosen from the series consisting of
N(R.sup.2) and O, in another embodiment from the series consisting
of N(R.sup.2) and S, in another embodiment from the series
consisting of O and S, in another embodiment D is N(R.sup.2), in
another embodiment D is O, in another embodiment D is S. In one
embodiment of the invention, the group E is C(R.sup.3), in another
embodiment E is N. In one embodiment of the invention, one or more
of the groups A, D and E have any one or some of their meanings and
any remaining groups A, D and E have all their meanings. For
example, in one embodiment A is chosen from the series consisting
of C(R.sup.1) and N, D is N(R.sup.2) and E is chosen from the
series consisting of C(R.sup.3) and N, in another embodiment A is
chosen from the series consisting of C(R.sup.1) and N, D is
N(R.sup.2) and E is N, in another embodiment A is C(R.sup.1), D is
N(R.sup.2) and E is chosen from the series consisting of C(R.sup.3)
and N, in another embodiment A is C(R.sup.1), D is N(R.sup.2) and E
is N, in another embodiment A is C(R.sup.1), D is chosen from the
series consisting of N(R.sup.2) and O and D is N, in another
embodiment A is N, D is chosen from the series consisting of from
N(R.sup.2), O and S and E is C(R.sup.3), in another embodiment A is
N, D is N(R.sup.2) and E is chosen from the series consisting of
C(R.sup.3) and N. In one embodiment of the invention, one of the
groups A and D is N and the other of the groups A and D is
C(R.sup.1) or C(R.sup.3), respectively, in another embodiment one
or both of the groups A and D are N and any remaining group A or D
is C(R.sup.1) or C(R.sup.3), respectively, in another embodiment
both of the groups A and D are N, and in another embodiment none of
the groups A and D is N.
[0025] In terms of formulae resulting from formula I by
incorporation of meanings of A, D or E, in one embodiment of the
invention a compound of the formula I is a compound of any one or
more of formulae I-1 to I-35, for example a compound of formula
I-1, or a compound of formula I-2, or a compound of formula I-6, or
a compound of formula I-9, or a compound of formula I-10, or a
compound of formula I-14, or a compound of formula I-17, or a
compound of formula I-19, or a compound of formula I-6 or formula
I-14, or a compound of formula I-11 or formula I-12, or a compound
of formula I-6 or formula I-10 or formula I-14, in any of its
stereoisomeric forms or a mixture of stereoisomeric forms in any
ratio, or a physiologically acceptable salt thereof, or a
physiologically acceptable solvate of any of them, wherein in the
compounds of formulae I-1 to I-35 the groups A, D, E, G, R.sup.1,
R.sup.2, R.sup.3, R.sup.10, R.sup.30, R.sup.40, R.sup.50 and
R.sup.60 are defined as in the compounds of formula I in general or
in any embodiment specified above or below.
##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008##
##STR00009##
[0026] In one embodiment of the invention, the group G is chosen
from the series consisting of R.sup.71--O--C(O)--,
R.sup.72--N(R.sup.73)--C(O)-- and tetrazol-5-yl, in another
embodiment from the series consisting of R.sup.71--O--C(O)-- and
R.sup.72--N(R.sup.73)--C(O)--, in another embodiment G is
R.sup.71--O--C(O)--, and in another embodiment G is
R.sup.72--N(R.sup.73)--C(O)--.
[0027] In one embodiment of the invention, the group R.sup.1 is
chosen from the series consisting of hydrogen, halogen,
(C.sub.1-C.sub.6)-alkyl, HO--, (C.sub.1-C.sub.6)-alkyl-O--, and
NC--, in another embodiment from the series consisting of hydrogen,
halogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O-- and
NC--, in another embodiment from the series consisting of hydrogen,
halogen, (C.sub.1-C.sub.6)-alkyl and NC--, in another embodiment
from the series consisting of hydrogen, halogen,
(C.sub.1-C.sub.6)-alkyl, HO-- and (C.sub.1-C.sub.6)-alkyl-O--, in
another embodiment from the series consisting of hydrogen, halogen,
(C.sub.1-C.sub.6)-alkyl and (C.sub.1-C.sub.6)-alkyl-O--, in another
embodiment from the series consisting of hydrogen, halogen and
(C.sub.1-C.sub.6)-alkyl, in another embodiment from the series
consisting of hydrogen and halogen, in another embodiment from the
series consisting of hydrogen, fluorine and chlorine, and in
another embodiment R.sup.1 is hydrogen. In one embodiment of the
invention, a (C.sub.1-C.sub.6)-alkyl group occurring in R.sup.1 is
a (C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment it is
methyl.
[0028] In one embodiment of the invention, the group R.sup.2 is
chosen from the series consisting of (C.sub.1-C.sub.7)-alkyl and
(C.sub.3-C.sub.7)-cycloalkyl-C.sub.sH.sub.2s--, in another
embodiment from the series consisting of
(C.sub.3-C.sub.7)-Cycloalkyl-C.sub.sH.sub.2s-- and
Ar--C.sub.sH.sub.2s--, in another embodiment R.sup.2 is
(C.sub.1-C.sub.7)-alkyl, in another embodiment R.sup.2 is
(C.sub.3-C.sub.7)-cycloalkyl-C.sub.sH.sub.2s--, and in another
embodiment R.sup.2 is Ar--C.sub.sH.sub.2s--. In one embodiment, s
is an integer chosen from the series consisting of 0, 1 and 2, in
another embodiment from the series consisting of 0 and 1, in
another embodiment from the series consisting of 1 and 2, in
another embodiment s is 0, and in another embodiment s is 1. In one
embodiment of the invention, R.sup.2 is Ar--C.sub.sH.sub.2s-- and s
is 0, i.e., R.sup.2 is the group Ar and the group D thus is the
group N(Ar). In one embodiment, the divalent alkanediyl group
C.sub.sH.sub.2s is a linear group. In one embodiment, a
(C.sub.1-C.sub.7)-alkyl group representing R.sup.2 is a
(C.sub.3-C.sub.7)-alkyl group, in another embodiment a
(C.sub.3-C.sub.6)-alkyl group. In one embodiment, a
(C.sub.3-C.sub.7)-cycloalkyl group occurring in R.sup.2 is a
(C.sub.3-C.sub.6)-cycloalkyl group, in another embodiment a
(C.sub.5-C.sub.6)-cycloalkyl group, in another embodiment a
cyclopropyl group. In one embodiment, a group Ar occurring in
R.sup.2 is chosen from the series consisting of phenyl and an
aromatic 5-membered or 6-membered heterocycle which comprises one
or two identical or different ring heteroatoms chosen from the
series consisting of nitrogen, oxygen and sulfur, which is bonded
via a ring carbon atom, in another embodiment from the series
consisting of phenyl and an aromatic 6-membered heterocycle which
comprises one or two nitrogen atoms as ring heteroatoms, in another
embodiment from the series consisting of phenyl, thiophenyl,
pyridinyl and pyrimidinyl, in another embodiment from the series
consisting of phenyl and thiophenyl, in another embodiment from the
series consisting of phenyl, pyridinyl and pyrimidinyl, in another
embodiment from the series consisting of phenyl and pyridinyl, and
in another embodiment a group Ar occurring in R.sup.2 is phenyl,
which groups all are optionally substituted as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, a group Ar
occurring in R.sup.2 is optionally substituted by one, two or three
identical or different substituents, in another embodiment it is
optionally substituted by one or two identical or different
substituents, in another embodiment it is optionally substituted by
one substituent, in another embodiment it is substituted by one,
two or three identical or different substituents, in another
embodiment it is substituted by one or two identical or different
substituents, and in another embodiment it is substituted by one
substituent. In one embodiment, the substituents which are
optionally present on a group Ar occurring in R.sup.2, are chosen
from the series consisting of halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.1-C.sub.6)-alkyl-O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--
and NC--, in another embodiment from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O-- and
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m--, in another embodiment from
the series consisting of halogen, (C.sub.1-C.sub.6)-alkyl and
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m--, in another embodiment from
the series consisting of halogen and (C.sub.1-C.sub.6)-alkyl, in
another embodiment from the series consisting of halogen, in
another embodiment from the series consisting of fluorine and
chlorine, in another embodiment from the series consisting of
fluorine, chlorine and methyl. In one embodiment of the invention,
a (C.sub.1-C.sub.6)-alkyl group occurring in R.sup.2 is a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment it is
methyl.
[0029] Examples of groups Ar which can occur in R.sup.2, and from
any one or more of which a group Ar occurring in R.sup.2 is chosen
in one embodiment of the invention, are phenyl, 2-fluoro-phenyl,
3-fluoro-phenyl, 4-fluoro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl,
4-chloro-phenyl, 3-bromo-phenyl, 4-bromo-phenyl,
2,3-dichloro-phenyl, 2,4-dichloro-phenyl, 2,5-dichloro-phenyl,
2,6-dichloro-phenyl, 3,4-dichloro-phenyl, 2,3-difluoro-phenyl,
2,4-difluoro-phenyl, 2,5-difluoro-phenyl, 2,6-difluoro-phenyl,
3,4-difluoro-phenyl, 2-chloro-6-fluoro-phenyl,
3,4,5-trifluoro-phenyl, 2-methyl-phenyl (o-tolyl), 3-methyl-phenyl
(m-tolyl), 4-methyl-phenyl (p-tolyl), 2,3-dimethyl-phenyl,
2,4-dimethyl-phenyl, 2,5-dimethyl-phenyl, 2,6-dimethyl-phenyl,
3,4-dimethyl-phenyl, 2-ethyl-phenyl, 3-ethyl-phenyl,
4-ethyl-phenyl, 3-isopropyl-phenyl, 3-tert-butyl-phenyl,
4-tert-butyl-phenyl, 3-trifluoromethyl-phenyl,
4-trifluoromethyl-phenyl, 2-fluoro-5-methyl-phenyl,
3-chloro-2-methyl-phenyl, 5-chloro-2-methyl-phenyl,
5-chloro-2-fluoro-3-methyl-phenyl,
2-fluoro-3-trifluoromethyl-phenyl,
2-fluoro-5-trifluoromethyl-phenyl,
4-fluoro-3-trifluoromethyl-phenyl,
5-fluoro-3-trifluoromethyl-phenyl,
3-chloro-4-trifluoromethyl-phenyl,
5-chloro-2-trifluoromethyl-phenyl,
5-chloro-3-trifluoromethyl-phenyl, 2-methoxy-phenyl,
3-methoxy-phenyl, 4-methoxy-phenyl, 3-ethoxy-phenyl,
3-propoxy-phenyl, 3-isopropoxy-phenyl, 4-tert-butoxy-phenyl,
3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl,
3-(2,2,2-trifluoroethoxy)-phenyl, 5-chloro-2-methoxy-phenyl,
3-chloro-4-methoxy-phenyl, 5-fluoro-3-isopropoxy-phenyl,
2-fluoro-3-trifluoromethoxy-phenyl, 4-methoxy-3,5-dimethyl-phenyl,
3-methoxy-5-trifluoromethyl-phenyl, 2,3-methylenedioxy-phenyl,
2,3-difluoromethylenedioxy-phenyl, 3,4-methylenedioxy-phenyl,
3,4-difluoromethylenedioxy-phenyl, 3-methylsulfanyl-phenyl,
3-ethylsulfanyl-phenyl, 3-trifluoromethylsulfanyl-phenyl,
3-methanesulfonyl-phenyl, 3-ethanesulfonyl-phenyl,
3-sulfamoyl-phenyl, 2-cyano-phenyl, 3-cyano-phenyl, 4-cyano-phenyl,
thiophen-2-yl, thiophen-3-yl, 3-chloro-thiophen-2-yl,
4-chloro-thiophen-2-yl, 5-chloro-thiophen-2-yl,
4,5-dichloro-thiophen-2-yl, 5-chloro-thiophen-3-yl,
2,5-dichloro-thiophen-3-yl, 4-methyl-thiophen-2-yl,
5-methyl-thiophen-3-yl, 4,5-dimethyl-thiophen-2-yl, pyridin-2-yl,
pyridin-3-yl, pyridin-4-yl, 2-chloro-pyridin-3-yl,
5-chloro-pyridin-2-yl, 6-chloro-pyridin-3-yl,
2-chloro-pyridin-4-yl, 2,6-dichloro-pyridin-3-yl,
6-methoxy-pyridin-3-yl, 2-chloro-6-methoxy-pyridin-3-yl.
[0030] In one embodiment of the invention, the group R.sup.3 is
chosen from the series consisting of hydrogen, halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O--, and NC--, in
another embodiment from the series consisting of hydrogen, halogen,
(C.sub.1-C.sub.6)-alkyl and NC--, in another embodiment from the
series consisting of hydrogen, halogen, (C.sub.1-C.sub.6)-alkyl and
(C.sub.1-C.sub.6)-alkyl-O--, in another embodiment from the series
consisting of hydrogen, halogen and (C.sub.1-C.sub.6)-alkyl, in
another embodiment from the series consisting of hydrogen and
halogen, in another embodiment from the series consisting of
hydrogen and (C.sub.1-C.sub.6)-alkyl, in another embodiment from
the series consisting of hydrogen, fluorine and chlorine, in
another embodiment R.sup.3 is hydrogen, and in another embodiment
R.sup.3 is (C.sub.1-C.sub.6)-alkyl. In one embodiment of the
invention, a (C.sub.1-C.sub.6)-alkyl group occurring in R.sup.3 is
a (C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment it is
methyl.
[0031] In one embodiment of the invention, the group R.sup.10 is
chosen from the series consisting of R.sup.1--O-- and
R.sup.12--N(R.sup.13)--C(O)--O--, in another embodiment from the
series consisting of R.sup.12--N(R.sup.13)--C(O)--O-- and
Het.sup.2-C(O)--O--, and in another embodiment R.sup.10 is
R.sup.11--O--. In one embodiment, the group Het.sup.2 which can
occur in the group R.sup.10, is a saturated 4-membered to
6-membered, in another embodiment a 5-membered or 6-membered, in
another embodiment a 5-membered, monocyclic heterocycle which,
besides the ring nitrogen via which Het.sup.2 is bonded, optionally
comprises one further ring heteroatom chosen from the series
nitrogen, oxygen and sulfur. In one embodiment, the group Het.sup.2
which can occur in the group R.sup.10, does not comprise a further
ring heteroatom besides the ring nitrogen atom via which Het.sup.2
is bonded. In one embodiment, the number of substituents which are
optionally present on a group Het.sup.2 which can occur in
R.sup.10, is one, two, three or four, in another embodiment one,
two or three, in another embodiment one or two, in another
embodiment one, and in another embodiment such a group Het.sup.2 is
unsubstituted. In one embodiment, the substituents which are
optionally present on a group Het.sup.2 which can occur in the
group R.sup.10, are chosen from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl, HO-- and (C.sub.1-C.sub.4)-alkyl-O--, in
another embodiment from the series consisting of
(C.sub.1-C.sub.4)-alkyl, HO-- and (C.sub.1-C.sub.4)-alkyl-O--, in
another embodiment from the series consisting of
(C.sub.1-C.sub.4)-alkyl and HO-- and (C.sub.1-C.sub.4)-alkyl-O--,
in another embodiment they are (C.sub.1-C.sub.4)-alkyl
substituents, and in another embodiment they are HO--
substituents.
[0032] In one embodiment of the invention, the group R.sup.11 is
chosen from the series consisting of hydrogen, R.sup.14,
(C.sub.3-C.sub.7)-cycloalkyl and Het.sup.3, in another embodiment
from the series consisting of hydrogen and R.sup.14, in another
embodiment from the series consisting of hydrogen, R.sup.14 and
(C.sub.3-C.sub.7)-cycloalkyl, in another embodiment from the series
consisting of (C.sub.3-C.sub.7)-cycloalkyl, Ar and Het.sup.3, in
another embodiment from the series consisting of
(C.sub.3-C.sub.7)-cycloalkyl and Het.sup.3, in another embodiment
R.sup.11 is hydrogen, in another embodiment R.sup.11 is R.sup.14,
and in another embodiment R.sup.11 is Ar. In one embodiment, a
group Ar representing R.sup.11 is phenyl which is optionally
substituted as indicated with respect to the compounds of formula I
in general or in any embodiment specified above or below. In one
embodiment, a group Ar representing R.sup.11 is optionally
substituted by one, two or three identical or different
substituents, in another embodiment it is optionally substituted by
one or two identical or different substituents, in another
embodiment it is optionally substituted by one substituent. In one
embodiment, the substituents which are optionally present on a
group Ar representing R.sup.1, are chosen from the series
consisting of halogen, (C.sub.1-C.sub.4)-alkyl,
(C.sub.1-C.sub.4)-alkyl-O-- and NC--, in another embodiment from
the series consisting of halogen, (C.sub.1-C.sub.4)-alkyl and
(C.sub.1-C.sub.4)-alkyl-O--, in another embodiment from the series
consisting of halogen and (C.sub.1-C.sub.4)-alkyl. In one
embodiment, a (C.sub.3-C.sub.7)-cycloalkyl group representing
R.sup.11 is a (C.sub.3-C.sub.6)-cycloalkyl group. In one
embodiment, a group Het.sup.3 representing R.sup.11 is a saturated
4-membered to 6-membered monocyclic heterocycle which comprises one
or two identical or different ring heteroatoms, in another
embodiment one ring heteroatom, which are chosen from the series
consisting of nitrogen, oxygen and sulfur, in another embodiment it
comprises one ring heteroatom chosen from the series consisting of
nitrogen and oxygen, in another embodiment one ring heteroatom
chosen from the series consisting of oxygen and sulfur, and in
another embodiment it comprises one oxygen atom as ring heteroatom,
wherein the heterocycle is bonded via a ring carbon atom and is
optionally substituted by one, two, three or four, in another
embodiment by one or two, identical or different substituents
chosen from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl and oxo, in another embodiment from the
series consisting of fluorine and (C.sub.1-C.sub.4)-alkyl.
[0033] In one embodiment of the invention, the groups R.sup.12 and
R.sup.13 are independently of each other chosen from the series
consisting of hydrogen and R.sup.15, in another embodiment from the
series consisting of R.sup.15 and Ar, and in another embodiment
they are identical or different groups R.sup.15. In one embodiment,
one of the groups R.sup.12 and R.sup.13 is chosen from the series
consisting of R.sup.15 and Ar, and the other is a group R.sup.15.
In one embodiment, a group Ar representing R.sup.12 or R.sup.13 is
phenyl which is optionally substituted by one or two, in another
embodiment by one, identical or different substituents chosen from
the series consisting of halogen and (C.sub.1-C.sub.4)-alkyl, and
in another embodiment it is unsubstituted phenyl.
[0034] In one embodiment of the invention, the
(C.sub.1-C.sub.10)-alkyl group representing the group R.sup.14 is a
(C.sub.1-C.sub.8)-alkyl group, in another embodiment a
(C.sub.1-C.sub.7)-alkyl group, in another embodiment a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.3)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment a methyl
group, in another embodiment a (C.sub.4-C.sub.8)-alkyl group, in
another embodiment a (C.sub.4-C.sub.7)-alkyl group, in another
embodiment a (C.sub.5-C.sub.7)-alkyl group, in another embodiment a
C.sub.6-alkyl group, wherein all these alkyl groups are linear or
branched as applies to alkyl groups in the compounds of the formula
I in general, and are optionally substituted by one or more
identical or different substituents as indicated with respect to
the compounds of formula I in general or in any embodiment
specified above or below. In one embodiment of the invention, the
number of optional substituents in an alkyl group representing
R.sup.14 is one, two, three or four, in another embodiment one, two
or three, in another embodiment one or two, in another embodiment
one. In one embodiment, an alkyl group representing R.sup.14 is
unsubstituted, and in another embodiment it is substituted by one,
two, three or four, in another embodiment by one, two or three, in
another embodiment by one or two, in another embodiment by one
substituent as indicated.
[0035] In one embodiment, a (C.sub.3-C.sub.7)-cycloalkyl group
occurring as a substituent on an alkyl group representing R.sup.14
is a (C.sub.3-C.sub.6)-cycloalkyl group, in another embodiment it
is a cyclopropyl group. In one embodiment, a group Ar occurring as
a substituent on an alkyl group representing R.sup.14 is phenyl or
an aromatic 5-membered or 6-membered monocyclic heterocycle which
comprises one or two identical or different ring heteroatoms chosen
from the series consisting of nitrogen, oxygen and sulfur, and in
another embodiment comprises one nitrogen atom as ring heteroatom
and in the case of a 5-membered heterocycle one additional ring
heteroatom chosen from the series consisting of nitrogen, oxygen
and sulfur, and in another embodiment a group Ar occurring as a
substituent in an alkyl group representing R.sup.14 is chosen from
phenyl, pyrazolyl, isoxazolyl and thiazolyl, wherein all these
groups Ar are optionally substituted by one or more identical or
different substituents as indicated with respect to the compounds
of formula I in general or in any embodiment specified above or
below. In one embodiment, the number of optional substituents on a
group Ar occurring as a substituent in an alkyl group representing
R.sup.14 is one, two or three, in another embodiment one or two, in
another embodiment one. In one embodiment, the substituents which
are optionally present on a group Ar occurring as a substituent in
an alkyl group representing R.sup.14, are chosen from the series
consisting of halogen, (C.sub.1-C.sub.4)-alkyl,
(C.sub.1-C.sub.4)-alkyl-O-- and NC--, in another embodiment from
the series consisting of halogen, (C.sub.1-C.sub.4)-alkyl and
(C.sub.1-C.sub.4)-alkyl-O--, in another embodiment from the series
consisting of halogen and (C.sub.1-C.sub.4)-alkyl, and in another
embodiment they are (C.sub.1-C.sub.4)-alkyl groups.
[0036] In one embodiment, a group Het.sup.1 occurring as a
substituent on an alkyl group representing R.sup.14 is a saturated
or unsaturated 4-membered to 6-membered heterocycle, in another
embodiment a 5-membered or 6-membered heterocycle, which comprises
a ring nitrogen atom via which Het.sup.1 is bonded and optionally
one further ring heteroatom chosen from the series consisting of
nitrogen, oxygen and sulfur, which is optionally substituted as
indicated with respect to the compounds of formula I in general or
in any embodiment specified above or below. In one embodiment, a
group Het.sup.1 occurring as a substituent on an alkyl group
representing R.sup.14 does not comprise any further ring heteroatom
besides the ring nitrogen atom via which Het.sup.1 is bonded. In
one embodiment, a group Het.sup.1 occurring as a substituent on an
alkyl group representing R.sup.14 is saturated, in another
embodiment it is unsaturated. In one embodiment, the number of
substituents which are optionally present on a group Het.sup.1
occurring as a substituent on an alkyl group representing R.sup.14
is one, two, three or four, in another embodiment one, two or
three, in another embodiment one or two, in another embodiment one.
In one embodiment, the substituents which are optionally present on
a group Het.sup.1 occurring as a substituent on an alkyl group
representing R.sup.14 are chosen from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, HO--, (C.sub.1-C.sub.4)-alkyl-O--
and oxo, in another embodiment from the series consisting of
fluorine, (C.sub.1-C.sub.4)-alkyl, HO-- and oxo, in another
embodiment from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl and oxo, in another embodiment from the
series consisting of (C.sub.1-C.sub.4)-alkyl and oxo, and in
another embodiment they are oxo substituents. In one embodiment,
the number of oxo substituents which are optionally present on a
group Het.sup.1 occurring as a substituent on an alkyl group
representing R.sup.14, is not greater than two, and in another
embodiment it is not greater than one.
[0037] In one embodiment, a group Het.sup.1 occurring in the
substituent Het.sup.1-C(O)-- on an alkyl group representing
R.sup.14 is a 4-membered to 6-membered heterocycle, in another
embodiment a 5-membered or 6-membered heterocycle, which is
saturated or unsaturated and comprises a ring nitrogen atom via
which Het.sup.1 is bonded and optionally one further ring
heteroatom chosen from the series consisting of nitrogen, oxygen
and sulfur, and which is optionally substituted as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, a group
Het.sup.1 occurring in the substituent Het.sup.1-C(O)-- on an alkyl
group representing R.sup.14 does not comprise any further ring
heteroatom besides the ring nitrogen atom via which Het.sup.1 is
bonded. In one embodiment, a group Het.sup.1 occurring in the
substituent Het.sup.1-C(O)-- on an alkyl group representing
R.sup.14 is saturated or comprises one double bond within the ring,
and in another embodiment it is saturated. In one embodiment, the
number of substituents which are optionally present on a group
Het.sup.1 occurring in the substituent Het.sup.1-C(O)-- on an alkyl
group representing R.sup.14 is one, two, three or four, in another
embodiment one, two or three, in another embodiment one or two, in
another embodiment one. In one embodiment, the substituents which
are optionally present on a group Het.sup.1 occurring in the
substituent Het.sup.1-C(O)-- on an alkyl group representing
R.sup.14 are chosen from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl, HO--, (C.sub.1-C.sub.4)-alkyl-O-- and oxo,
in another embodiment from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl, HO-- and oxo, in another embodiment from
the series consisting of fluorine, (C.sub.1-C.sub.4)-alkyl and oxo,
in another embodiment from (C.sub.1-C.sub.4)-alkyl and oxo, in
another embodiment they are oxo substituents, and in another
embodiment they are (C.sub.1-C.sub.4)-alkyl substituents. In one
embodiment, the number of oxo substituents which are optionally
present on a group Het.sup.1 occurring in the substituent
Het.sup.1-C(O)-- on an alkyl group representing R.sup.14, is not
greater than two, and in another embodiment it is not greater than
one, and in another embodiment no oxo substituents are present on
such a group Het.sup.1.
[0038] In one embodiment, a group Het.sup.3 occurring as a
substituent on an alkyl group representing R.sup.14 is a saturated
4-membered to 6-membered monocyclic heterocycle which comprises one
or two identical or different ring heteroatoms, and in another
embodiment comprises one ring heteroatom, which are chosen from the
series consisting of nitrogen, oxygen and sulfur, and is bonded via
a ring carbon atom and is optionally substituted as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, the ring
heteroatoms in a group Het.sup.3 occurring as a substituent on an
alkyl group representing R.sup.14 are chosen from the series
consisting of nitrogen and oxygen, in another embodiment from the
series consisting of oxygen and sulfur, in another embodiment they
are nitrogen atoms, and in another embodiment they are oxygen
atoms. In one embodiment, the number of substituents which are
optionally present on a group Het.sup.3 occurring as a substituent
on an alkyl group representing R.sup.14 is one, two, three or four,
in another embodiment one, two or three, in another embodiment one
or two, in another embodiment one. In one embodiment, the
substituents which are optionally present on a group Het.sup.3
occurring as a substituent on an alkyl group representing R.sup.14
are chosen from the series consisting of fluorine and
(C.sub.1-C.sub.4)-alkyl, in another embodiment from the series
consisting of (C.sub.1-C.sub.4)-alkyl and oxo, in another
embodiment they are (C.sub.1-C.sub.4)-alkyl substituents, and in
another embodiment they are oxo substituents. In one embodiment,
the number of oxo substituents which are optionally present on a
group Het.sup.3 occurring as a substituent on an alkyl group
representing R.sup.14, is not greater than two, and in another
embodiment it is not greater than one.
[0039] In one embodiment, the substituents which are optionally
present on an alkyl group representing R.sup.14 are chosen from the
series consisting of halogen, HO--, R.sup.16--O--, oxo,
(C.sub.3-C.sub.7)-cycloalkyl, Ar, Het.sup.1, Het.sup.3,
H.sub.2N--C(O)--, (C.sub.1-C.sub.4)-alkyl-NH--C(O)--,
di((C.sub.1-C.sub.4)-alkyl)N--C(O)-- and Het.sup.1-C(O)--, in
another embodiment from the series consisting of halogen, HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl, Het.sup.1,
Het.sup.3, H.sub.2N--C(O)--, (C.sub.1-C.sub.4)-alkyl-NH--C(O)--,
di((C.sub.1-C.sub.4)-alkyl)N--C(O)-- and Het.sup.1-C(O)--, in
another embodiment from the series consisting of halogen, HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl, Het.sup.1,
Het.sup.3, di((C.sub.1-C.sub.4)-alkyl)N--C(O)-- and
Het.sup.1-C(O)--, in another embodiment from the series consisting
of halogen, HO--, R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl,
Het.sup.1 and Het.sup.3, in another embodiment from the series
consisting of halogen, HO--, R.sup.16--O--, oxo,
(C.sub.3-C.sub.7)-cycloalkyl, Ar, Het.sup.1 and Het.sup.3, in
another embodiment from the series consisting of HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl, Ar, Het.sup.1,
di((C.sub.1-C.sub.4)-alkyl)N--C(O)-- and Het.sup.1-C(O)--, in
another embodiment from the series consisting of HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-Cycloalkyl, Ar,
di((C.sub.1-C.sub.4)-alkyl)N--C(O)-- and Het.sup.1-C(O)--, in
another embodiment from the series consisting of HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl and Ar, in another
embodiment from the series consisting of HO--, R.sup.16--O--, oxo,
(C.sub.3-C.sub.7)-cycloalkyl, di((C.sub.1-C.sub.4)-alkyl)N--C(O)--
and Het.sup.1-C(O)--, in another embodiment from the series
consisting of HO--, R.sup.16--O--, oxo,
(C.sub.3-C.sub.7)-Cycloalkyl, Het.sup.1 and Het.sup.3, in another
embodiment from the series consisting of HO--, R.sup.16--O--, oxo,
(C.sub.3-C.sub.7)-cycloalkyl and Het.sup.3, in another embodiment
from the series consisting of HO--, oxo,
(C.sub.3-C.sub.7)-cycloalkyl and Het.sup.3, in another embodiment
from the series consisting of HO--, oxo and
(C.sub.3-C.sub.7)-cycloalkyl, in another embodiment from the series
consisting of HO--, oxo and Het.sup.3, in another embodiment from
the series consisting of HO-- and oxo, in another embodiment from
the series consisting of HO--, R.sup.16--O--,
(C.sub.3-C.sub.7)-cycloalkyl and Het.sup.3, in another embodiment
from the series consisting of HO--, (C.sub.3-C.sub.7)-cycloalkyl
and Het.sup.3, in another embodiment from the series consisting of
HO-- and (C.sub.3-C.sub.7)-cycloalkyl, in another embodiment from
the series consisting of HO-- and Het.sup.3, in another embodiment
they are HO-- substituents, and in another embodiment they are oxo
substituents. In one embodiment, the number of oxo substituents
which are optionally present on an alkyl group representing
R.sup.14, is not greater than two, and in another embodiment it is
not greater than one. In one embodiment, halogen atoms occurring as
substituents on an alkyl group representing R.sup.14, are chosen
from the series consisting of fluorine and chlorine atoms, and in
another embodiment they are fluorine atoms and, besides being
substituted by an other substituents, in this latter embodiment an
alkyl group representing R.sup.14 is thus optionally substituted by
fluorine substituents as applies to alkyl groups in the compounds
of the formula I in general.
[0040] Examples of groups which can represent R.sup.14, and from
any one or more of which R.sup.14 is chosen in one embodiment of
the invention, are methyl, ethyl, propyl, isopropyl, butyl,
isobutyl, cyclopropylmethyl, benzyl, 2-hydroxy-ethyl,
2-hydroxy-propyl, 2-hydroxy-butyl, 2-hydroxy-2-methyl-propyl,
2-hydroxy-2-methyl-butyl, 2-hydroxy-3-methyl-butyl,
2-hydroxy-2,3-dimethyl-butyl, 2-hydroxy-3,3-dimethyl-butyl,
2-ethyl-2-hydroxy-butyl, 2-hydroxy-2,3,3-trimethyl-butyl,
2-ethyl-2-hydroxy-3-methyl-butyl,
2-ethyl-2-hydroxy-3,3-dimethyl-butyl,
2-cyclopropyl-2-hydroxy-ethyl, 2-cyclopropyl-2-hydroxy-propyl,
2-cyclopropyl-2-hydroxy-butyl, 2-oxo-propyl, 2-oxo-butyl,
3-methyl-2-oxo-butyl, 3,3-dimethyl-2-oxo-butyl,
2-cyclopropyl-2-oxo-ethyl.
[0041] In case the optionally substituted alkyl group representing
R.sup.14, including the examples of groups listed afore which can
represent R.sup.14, contains a chiral carbon atom, the compound of
the formula I can be present with respect to this carbon atom in
any of it stereoisomeric forms, i.e. in R configuration or in S
configuration, or in the form of a mixture of the stereoisomeric
forms in any ratio, for example as a mixture of the two
stereoisomeric forms in a molar ratio of 1:1, as applies to all
chiral carbon atoms in the compounds of the formula I. In one
embodiment of the invention, the compound of the formula I has at a
chiral carbon atom in R.sup.14 pure stereochemical configuration,
either R configuration or S configuration, or essentially pure
stereochemical configuration, for example with a molar ratio of the
two configurations of 99:1 or greater.
[0042] In one embodiment of the invention, the
(C.sub.1-C.sub.6)-alkyl group representing the group R.sup.15 is a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment a methyl
group, wherein all these alkyl groups are optionally substituted by
one or more identical or different substituents as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment of the
invention, the number of optional substituents in an alkyl group
representing R.sup.15 is one or two, in another embodiment one. In
one embodiment, the alkyl group representing R.sup.15 is
unsubstituted. In one embodiment, the substituents which are
optionally present on an alkyl group representing R.sup.15 are
chosen from the series consisting of HO-- and
(C.sub.1-C.sub.4)-alkyl-O--.
[0043] In one embodiment of the invention, the
(C.sub.1-C.sub.6)-alkyl group representing the group R.sup.16 is a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.3)-alkyl group, in another embodiment a
(C.sub.2-C.sub.3)-alkyl group, in another embodiment an ethyl
group, in another embodiment a methyl group, wherein all these
alkyl groups are optionally substituted by one or more identical or
different substituents as indicated with respect to the compounds
of formula I in general or in any embodiment specified above or
below. In one embodiment of the invention, the number of optional
substituents in an alkyl group representing R.sup.16 is one or two,
in another embodiment one. In one embodiment, an alkyl group
representing R.sup.14 is unsubstituted, in another embodiment it is
substituted by one or two identical or different substituents, in
another embodiment it is substituted by one substituent. In one
embodiment, the substituents which are optionally present on an
alkyl group representing R.sup.15 are chosen from the series
consisting of HO-- and (C.sub.1-C.sub.4)-alkyl-O--, in another
embodiment they are HO-- substituents, in another embodiment they
are (C.sub.1-C.sub.4)-alkyl-O-- substituents, and in another
embodiment they are (C.sub.1-C.sub.2)-alkyl-O-- substituents.
[0044] In one embodiment of the invention, the group R.sup.30 is
chosen from the series consisting of R.sup.31,
(C.sub.3-C.sub.7)-Cycloalkyl and Het.sup.3-C.sub.uH.sub.2u--, in
another embodiment from the series consisting of
(C.sub.3-C.sub.7)-cycloalkyl, R.sup.32--C.sub.uH.sub.2u-- and
Het.sup.3-C.sub.uH.sub.2u--, in another embodiment from the series
consisting of R.sup.32--C.sub.uH.sub.2u-- and
Het.sup.3-C.sub.uH.sub.2u--, in another embodiment R.sup.30 is
R.sup.32--C.sub.uH.sub.2u--, and in another embodiment R.sup.30 is
R.sup.31. In one embodiment, u is an integer chosen from the series
consisting of 0, 1 and 2, in another embodiment from the series
consisting of 0 and 1, in another embodiment from the series
consisting of 1 and 2, in another embodiment u is 0, and in another
embodiment u is 1. In one embodiment, R.sup.30 is
R.sup.32--C.sub.uH.sub.2u-- and u is 0, i.e., in this embodiment
R.sup.30 is chosen from the series consisting of phenyl and an
aromatic 5-membered or 6-membered monocyclic heterocycle which
comprises one, two or three identical or different ring heteroatoms
chosen from the series consisting of nitrogen, oxygen and sulfur
and is bonded via a ring carbon atom, wherein the phenyl and the
heterocycle all are optionally substituted as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, the
divalent alkanediyl group C.sub.uH.sub.2u is a linear group.
[0045] In one embodiment, the (C.sub.3-C.sub.7)-Cycloalkyl group
representing R.sup.30 is a (C.sub.3-C.sub.6)-cycloalkyl group, in
another embodiment a (C.sub.5-C.sub.6)-cycloalkyl group, in another
embodiment a cyclopropyl group. In one embodiment, a group
Het.sup.3 occurring in R.sup.30 is a saturated 4-membered to
6-membered monocyclic heterocycle, in another embodiment a
saturated 5-membered or 6-membered heterocycle, in another
embodiment a saturated 6-membered heterocycle, which comprises one
or two identical or different ring heteroatoms, and in another
embodiment comprises one ring heteroatom, which are chosen from the
series consisting of nitrogen, oxygen and sulfur, and is bonded via
a ring carbon atom and is optionally substituted as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, the ring
heteroatoms in a group Het.sup.3 occurring in R.sup.30 are chosen
from the series consisting of nitrogen and oxygen, in another
embodiment from the series consisting of oxygen and sulfur, in
another embodiment they are nitrogen atoms, and in another
embodiment they are oxygen atoms. In one embodiment, the number of
substituents which are optionally present on a group Het.sup.3
occurring in R.sup.30 is one, two, three or four, in another
embodiment one, two or three, in another embodiment one or two, in
another embodiment one, and in another embodiment a group Het.sup.3
occurring in R.sup.30 is unsubstituted. In one embodiment, the
substituents which are optionally present on a group Het.sup.3
occurring in R.sup.30 are chosen from the series consisting of
fluorine and (C.sub.1-C.sub.4)-alkyl, in another embodiment they
are (C.sub.1-C.sub.4)-alkyl substituents.
[0046] In one embodiment of the invention, the
(C.sub.1-C.sub.10)-alkyl group representing R.sup.31 is a
(C.sub.1-C.sub.8)-alkyl group, in another embodiment a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.3)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment a methyl
group, in another embodiment a (C.sub.4-C.sub.8)-alkyl group, in
another embodiment a (C.sub.5-C.sub.8)-alkyl group, wherein all
these alkyl groups are optionally substituted by one or more
identical or different substituents as indicated with respect to
the compounds of formula I in general or in any embodiment
specified above or below. In one embodiment of the invention, the
number of optional substituents in an alkyl group representing
R.sup.31 is one, two or three, in another embodiment one or two, in
another embodiment one. In one embodiment, an alkyl group
representing R.sup.31 is unsubstituted, and in another embodiment
it is substituted by one, two or three, in another embodiment by
one or two, in another embodiment by one substituent as indicated.
In one embodiment, the optional substituents on an alkyl group
representing R.sup.31 are chosen from the series consisting of
halogen, (C.sub.3-C.sub.7)-cycloalkyl, (C.sub.1-C.sub.6)-alkyl-O--
and NC--, in another embodiment from the series consisting of
halogen, (C.sub.3-C.sub.7)-cycloalkyl and
(C.sub.1-C.sub.6)-alkyl-O--, in another embodiment from the series
consisting of halogen and (C.sub.3-C.sub.7)-cycloalkyl, and in
another embodiment they are (C.sub.3-C.sub.7)-cycloalkyl
substituents. In one embodiment, halogen atoms occurring as
substituents on an alkyl group representing R.sup.31, are chosen
from the series consisting of fluorine and chlorine atoms, and in
another embodiment they are fluorine atoms and, besides being
substituted by an other substituents, in this latter embodiment an
alkyl group representing R.sup.31 is thus optionally substituted by
fluorine substituents as applies to alkyl groups in the compounds
of the formula I in general. In one embodiment, a
(C.sub.3-C.sub.7)-cycloalkyl group occurring as a substituent on an
alkyl group representing R.sup.30 is a (C.sub.3-C.sub.6)-cycloalkyl
group, in another embodiment a (C.sub.5-C.sub.6)-cycloalkyl group,
in another embodiment a cyclopropyl group.
[0047] In one embodiment of the invention, the group R.sup.32 is
chosen from the series consisting of phenyl and an aromatic
5-membered or 6-membered monocyclic heterocycle which comprises one
or two identical or different ring heteroatoms, in another
embodiment one ring heteroatom, which are chosen from the series
consisting of nitrogen, oxygen and sulfur, and is bonded via a ring
carbon atom, in another embodiment from the series consisting of
phenyl and an aromatic 6-membered monocyclic heterocycle which
comprises one or two nitrogen atoms as ring heteroatoms, wherein
the phenyl and the heterocycle all are optionally substituted by
one or more identical or different substituents as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, the ring
heteroatoms in an aromatic heterocycle representing R.sup.32 are
chosen from the series consisting of nitrogen and sulfur, in
another embodiment they are nitrogen atoms. In one embodiment,
R.sup.32 is chosen from the series consisting of phenyl and an
aromatic 6-membered heterocycle as defined, in another embodiment
R.sup.32 is a 6-membered monocyclic heterocycle as defined, in
another embodiment R.sup.32 is chosen from the series consisting of
phenyl, thiophenyl and pyridinyl, in another embodiment from the
series consisting of phenyl and pyridinyl, in another embodiment
R.sup.32 is phenyl, and in another embodiment R.sup.32 is
pyridinyl, all of which are optionally substituted by one or more
identical or different substituents as indicated with respect to
the compounds of formula I in general or in any embodiment
specified above or below. In one embodiment, the number of
substituents which are optionally present on a phenyl group and an
aromatic heterocycle representing R.sup.32 is one, two, three or
four, in another embodiment one, two or three, in another
embodiment one or two, in another embodiment one.
[0048] In one embodiment, the substituents which are optionally
present on a phenyl group and an aromatic heterocycle representing
R.sup.32, in particular on a phenyl group, are chosen from the
series the series consisting of from halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
H.sub.2N--S(O).sub.2--, (C.sub.1-C.sub.4)-alkyl-NH--S(O).sub.2--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--,
(C.sub.1-C.sub.6)-alkyl-NH--, di((C.sub.1-C.sub.6)-alkyl)N--,
Het.sup.1, (C.sub.1-C.sub.4)-alkyl-C(O)--NH--, Ar--C(O)--NH--,
(C.sub.1-C.sub.4)-alkyl-S(O).sub.2--NH-- and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
H.sub.2N--S(O).sub.2--, (C.sub.1-C.sub.4)-alkyl-NH--S(O).sub.2--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--,
(C.sub.1-C.sub.6)-alkyl-NH--, di((C.sub.1-C.sub.6)-alkyl)N--,
Het.sup.1 and NC--, in another embodiment from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
(C.sub.1-C.sub.6)-alkyl-NH--, di((C.sub.1-C.sub.6)-alkyl)N--,
Het.sup.1 and NC--, in another embodiment from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--, Het.sup.1
and NC--, in another embodiment from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O-- and NC--, in another embodiment from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O-- and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--, H.sub.2N--,
di((C.sub.1-C.sub.6)-alkyl)N--, Het.sup.1,
(C.sub.1-C.sub.4)-alkyl-C(O)--NH--, Ar--C(O)--NH-- and NC--, in
another embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--, H.sub.2N--,
di((C.sub.1-C.sub.6)-alkyl)N--, Het.sup.1 and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--,
di((C.sub.1-C.sub.6)-alkyl)N--, Het.sup.1 and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--,
di((C.sub.1-C.sub.6)-alkyl)N--, Het.sup.1 and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, R.sup.33, (C.sub.1-C.sub.6)-alkyl-O-- and
R.sup.33--O--, in another embodiment from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, R.sup.33 and
(C.sub.1-C.sub.6)-alkyl-O--, in another embodiment from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl and R.sup.33, in
another embodiment from the series consisting of halogen and
(C.sub.1-C.sub.6)-alkyl. In one embodiment, in case that
substituents from the series consisting of
(C.sub.3-C.sub.7)-cycloalkyl, R.sup.33, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, Het.sup.1 and Ar--C(O)--NH-- are present on a
phenyl group and an aromatic heterocycle representing R.sup.32, not
more than two such substituents, in another embodiment not more
than one such substituent, are present, either without any other
substituents or together with any other substituents.
[0049] In one embodiment, a (C.sub.1-C.sub.6)-alkyl group occurring
in a substituent on a phenyl group and an aromatic heterocycle
representing R.sup.32 is a (C.sub.1-C.sub.4)-alkyl group, in
another embodiment a (C.sub.1-C.sub.3)-alkyl group, in another
embodiment a (C.sub.1-C.sub.2)-alkyl group, in another embodiment a
methyl group. In one embodiment, a (C.sub.3-C.sub.7)-cycloalkyl
group occurring as a substituent on a phenyl group and an aromatic
heterocycle representing R.sup.32 is a (C.sub.3-C.sub.6)-cycloalkyl
group, in another embodiment a (C.sub.3-C.sub.5)-cycloalkyl group,
in another embodiment a (C.sub.3-C.sub.4)-cycloalkyl group, in
another embodiment it is a cyclopropyl group. In one embodiment, a
group Ar occurring in a substituent on a phenyl group and an
aromatic heterocycle representing R.sup.32 is chosen from the
series consisting of phenyl and an aromatic 5-membered or
6-membered heterocycle which comprises one or two identical or
different ring heteroatoms, in another embodiment one ring
heteroatom, chosen from the series consisting of nitrogen, oxygen
and sulfur, which is bonded via a ring carbon atom, and in another
embodiment it is a phenyl group, which groups all are optionally
substituted as indicated with respect to the compounds of formula I
in general or in any embodiment specified above or below. In one
embodiment, the number of optional substituents on a group Ar
occurring in a substituent on a phenyl group and an aromatic
heterocycle representing R.sup.32 is one or two, in another
embodiment one, and the optional substituents are chosen from the
series consisting of halogen, (C.sub.1-C.sub.4)-alkyl,
(C.sub.1-C.sub.4)-alkyl-O--, (C.sub.1-C.sub.4)-alkyl-S(O).sub.m--
and NC--, in another embodiment from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkyl-O--,
in another embodiment from the series consisting of halogen and
(C.sub.1-C.sub.4)-alkyl, and in another embodiment such a group Ar
is unsubstituted.
[0050] In one embodiment, a group Het.sup.1 occurring as a
substituent on a phenyl group or an aromatic heterocycle
representing R.sup.32 is a saturated or unsaturated 4-membered to
6-membered monocyclic heterocycle, in another embodiment a
5-membered or 6-membered heterocycle, which comprises a ring
nitrogen atom via which Het.sup.1 is bonded and optionally one or
two further ring heteroatoms, in another embodiment one further
ring heteroatom, which are chosen from the series consisting of
nitrogen, oxygen and sulfur, which is optionally substituted as
indicated with respect to the compounds of formula I in general or
in any embodiment specified above or below. In one embodiment, a
group Het.sup.1 occurring as a substituent on a phenyl group or an
aromatic heterocycle representing R.sup.32 does not comprise any
further ring heteroatom besides the ring nitrogen atom via which
Het.sup.1 is bonded. In one embodiment, a group Het.sup.1 occurring
as a substituent on a phenyl group or an aromatic heterocycle
representing R.sup.32 is saturated, in another embodiment it is
unsaturated. In one embodiment, the number of substituents which
are optionally present on a group Het.sup.1 occurring as a
substituent on a phenyl group or an aromatic heterocycle
representing R.sup.32 is one, two, three or four, in another
embodiment one, two or three, in another embodiment one or two, in
another embodiment one, and in another embodiment such a group
Het.sup.1 is unsubstituted. In one embodiment, the substituents
which are optionally present on a group Het.sup.1 occurring as a
substituent on a phenyl group or an aromatic heterocycle
representing R.sup.32 are chosen from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, HO--, (C.sub.1-C.sub.4)-alkyl-O--
and oxo, in another embodiment from the series consisting of
fluorine, (C.sub.1-C.sub.4)-alkyl, HO-- and oxo, in another
embodiment from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl and oxo, and in another embodiment they are
(C.sub.1-C.sub.4)-alkyl substituents.
[0051] Examples of groups R.sup.32 from any one or more of which
R.sup.32 is chosen in one embodiment of the invention, are phenyl,
2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-chloro-phenyl,
3-chloro-phenyl, 4-chloro-phenyl, 3-bromo-phenyl, 4-bromo-phenyl,
2,3-dichloro-phenyl, 2,4-dichloro-phenyl, 2,5-dichloro-phenyl,
2,6-dichloro-phenyl, 3,4-dichloro-phenyl, 2,3-difluoro-phenyl,
2,4-difluoro-phenyl, 2,5-difluoro-phenyl, 2,6-difluoro-phenyl,
3,4-difluoro-phenyl, 2-chloro-6-fluoro-phenyl,
3,4,5-trifluoro-phenyl, 2-methyl-phenyl (o-tolyl), 3-methyl-phenyl
(m-tolyl), 4-methyl-phenyl (p-tolyl), 2,3-dimethyl-phenyl,
2,4-dimethyl-phenyl, 2,5-dimethyl-phenyl, 2,6-dimethyl-phenyl,
3,4-dimethyl-phenyl, 2-ethyl-phenyl, 3-ethyl-phenyl,
4-ethyl-phenyl, 3-isopropyl-phenyl, 3-tert-butyl-phenyl,
4-tert-butyl-phenyl, 3-trifluoromethyl-phenyl,
4-trifluoromethyl-phenyl, 2-fluoro-5-methyl-phenyl,
3-chloro-2-methyl-phenyl, 5-chloro-2-methyl-phenyl,
5-chloro-2-fluoro-3-methyl-phenyl,
2-fluoro-3-trifluoromethyl-phenyl,
2-fluoro-5-trifluoromethyl-phenyl,
4-fluoro-3-trifluoromethyl-phenyl,
5-fluoro-3-trifluoromethyl-phenyl,
3-chloro-4-trifluoromethyl-phenyl,
5-chloro-2-trifluoromethyl-phenyl,
5-chloro-3-trifluoromethyl-phenyl, 2-methoxy-phenyl,
3-methoxy-phenyl, 4-methoxy-phenyl, 3-ethoxy-phenyl,
3-propoxy-phenyl, 3-isopropoxy-phenyl, 4-tert-butoxy-phenyl,
3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl,
3-(2,2,2-trifluoroethoxy)-phenyl, 5-chloro-2-methoxy-phenyl,
3-chloro-4-methoxy-phenyl, 5-fluoro-3-isopropoxy-phenyl,
2-fluoro-3-trifluoromethoxy-phenyl, 4-methoxy-3,5-dimethyl-phenyl,
3-methoxy-5-trifluoromethyl-phenyl, 2,3-methylenedioxy-phenyl,
2,3-difluoromethylenedioxy-phenyl, 3,4-methylenedioxy-phenyl,
3,4-difluoromethylenedioxy-phenyl, 3-methylsulfanyl-phenyl,
3-ethylsulfanyl-phenyl, 3-trifluoromethylsulfanyl-phenyl,
3-methanesulfonyl-phenyl, 3-ethanesulfonyl-phenyl,
3-sulfamoyl-phenyl, 2-cyano-phenyl, 3-cyano-phenyl, 4-cyano-phenyl,
thiophen-2-yl, thiophen-3-yl, 3-chloro-thiophen-2-yl,
4-chloro-thiophen-2-yl, 5-chloro-thiophen-2-yl,
4,5-dichloro-thiophen-2-yl, 5-chloro-thiophen-3-yl,
2,5-dichloro-thiophen-3-yl, 4-methyl-thiophen-2-yl,
5-methyl-thiophen-3-yl, 4,5-dimethyl-thiophen-2-yl, pyridin-2-yl,
pyridin-3-yl, pyridin-4-yl, 2-chloro-pyridin-3-yl,
5-chloro-pyridin-2-yl, 6-chloro-pyridin-3-yl,
2-chloro-pyridin-4-yl, 2,6-dichloro-pyridin-3-yl,
6-methoxy-pyridin-3-yl, 2-chloro-6-methoxy-pyridin-3-yl.
[0052] In one embodiment of the invention, the group R.sup.33 is
chosen from the series consisting of phenyl and an aromatic
5-membered or 6-membered monocyclic heterocycle which comprises one
or two identical or different ring heteroatoms, in another
embodiment one ring heteroatom, which is chosen from the series
consisting of nitrogen, oxygen and sulfur, and is bonded via a ring
carbon atom, wherein the phenyl and the heterocycle all are
optionally substituted by one or more identical or different
substituents as indicated with respect to the compounds of formula
I in general or in any embodiment specified above or below. In one
embodiment, the ring heteroatoms in an aromatic heterocycle
representing R.sup.33 are chosen from the series consisting of
nitrogen and sulfur, in another embodiment they are nitrogen atoms.
In one embodiment, R.sup.33 is chosen from the series consisting of
phenyl and an aromatic 6-membered heterocycle as defined, in
another embodiment from the series consisting of phenyl and an
aromatic 6-membered heterocycle which comprises one or two nitrogen
atoms as ring heteroatoms, in another embodiment R.sup.33 is a
6-membered monocyclic heterocycle as defined, in another embodiment
it is an aromatic 6-membered heterocycle which comprises one or two
nitrogen atoms as ring heteroatoms, in another embodiment R.sup.33
is chosen from the series consisting of phenyl, thiophenyl and
pyridinyl, in another embodiment from the series consisting of
phenyl and pyridinyl, in another embodiment R.sup.33 is phenyl, and
in another embodiment R.sup.33 is pyridinyl, all of which are
optionally substituted by one or more identical or different
substituents as indicated with respect to the compounds of formula
I in general or in any embodiment specified above or below. In one
embodiment, the number of substituents which are optionally present
on a phenyl group and an aromatic heterocycle representing R.sup.33
is one, two or three, in another embodiment one or two, in another
embodiment one.
[0053] In one embodiment, the substituents which are optionally
present on a phenyl group and an aromatic heterocycle representing
R.sup.33, are chosen from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, HO--,
(C.sub.1-C.sub.6)-alkyl-O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
H.sub.2N--S(O).sub.2--, di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--
and NC--, in another embodiment from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl,
HO--, (C.sub.1-C.sub.6)-alkyl-O--, H.sub.2N--S(O).sub.2--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2-- and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, HO--,
(C.sub.1-C.sub.6)-alkyl-O-- and NC--, are chosen from the series
the series consisting of halogen, (C.sub.1-C.sub.4)-alkyl,
(C.sub.1-C.sub.4)-alkyl-O--, (C.sub.1-C.sub.4)-alkyl-S(O).sub.m--
and NC--, in another embodiment from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, (C.sub.1-C.sub.4)-alkyl-O-- and
NC--, in another embodiment from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkyl-O--, in another
embodiment from the series consisting of halogen and
(C.sub.1-C.sub.4)-alkyl. In one embodiment, a
(C.sub.1-C.sub.6)-alkyl group occurring in a substituent on a
phenyl group and an aromatic heterocycle representing R.sup.33 is a
(C.sub.1-C.sub.4)-alkyl group, in another embodiment a
(C.sub.1-C.sub.3)-alkyl group, in another embodiment a
(C.sub.1-C.sub.2)-alkyl group, in another embodiment a methyl
group. In one embodiment, a (C.sub.3-C.sub.7)-cycloalkyl group
occurring as a substituent on a phenyl group and an aromatic
heterocycle representing R.sup.32 is a (C.sub.3-C.sub.6)-cycloalkyl
group, in another embodiment a (C.sub.3-C.sub.5)-cycloalkyl group,
in another embodiment a (C.sub.3-C.sub.4)-cycloalkyl group, in
another embodiment it is a cyclopropyl group.
[0054] In one embodiment of the invention, the group R.sup.40 is
chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.2)-alkyl, in another embodiment from the series
consisting of hydrogen and methyl, and in another embodiment
R.sup.40 is hydrogen. In case R.sup.30 and R.sup.40 are different
and the carbon atom carrying R.sup.30 and R.sup.40 thus is chiral,
in one embodiment of the invention the compound of the formula I
has at this carbon atom pure stereochemical configuration, either R
configuration or S configuration, or essentially pure
stereochemical configuration, for example with a molar ratio of the
two configurations of 99:1 or greater. In case R.sup.30 is
R.sup.32--C.sub.uH.sub.2u-- and u is 0, i.e. R.sup.30 is phenyl or
an aromatic heterocycle as defined, R.sup.40 is hydrogen and
R.sup.50 is hydrogen, in one embodiment of the invention the
compound of the formula I has at the carbon atom carrying R.sup.30
and R.sup.40 pure S configuration, or essentially pure S
configuration, for example with a molar ratio of S configuration to
R configuration of 99:1 or greater.
[0055] In case R.sup.30 and R.sup.40 together are a divalent group
(CH.sub.2).sub.x, the two groups R.sup.30 and R.sup.40 together
with the carbon atom carrying them form a cycloalkane ring chosen
from cyclopropane, cyclobutane, cyclopentane and cyclohexane, which
carries the moieties --C(O)--NH and --C(R.sup.50)(R.sup.60)-G
depicted in formula I on the same ring carbon atom. In one
embodiment of the invention, the number of (C.sub.1-C.sub.4)-alkyl
substituents which are optionally present on the group
(CH.sub.2).sub.x, is one, two, three or four, in another embodiment
one or two, and in another embodiment no alkyl substituents are
present on the group (CH.sub.2).sub.x. In one embodiment, a
(C.sub.1-C.sub.4)-alkyl group occurring as a substituent on the
group (CH.sub.2).sub.x is a methyl group. In one embodiment, the
integer x is chosen from the series consisting of 2, 4 and 5, in
another embodiment from 4 and 5, in another embodiment x is 2, and
in another embodiment x is 4. In one embodiment of the invention,
R.sup.30 and R.sup.40 together cannot be (CH.sub.2).sub.x, and in
this embodiment R.sup.30 and R.sup.40 thus only have their other
meanings as defined.
[0056] In one embodiment of the invention, the group R.sup.50 is
chosen from the series consisting of hydrogen,
(C.sub.1-C.sub.4)-alkyl and HO--, in another embodiment from the
series consisting of hydrogen and (C.sub.1-C.sub.4)-alkyl, in
another embodiment from the series consisting of hydrogen and
(C.sub.1-C.sub.2)-alkyl, in another embodiment from the series
consisting of hydrogen and methyl, in another embodiment from the
series consisting of hydrogen and HO--, and in another embodiment
R.sup.50 is hydrogen.
[0057] In one embodiment of the invention, the group R.sup.60 is
chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.4)-alkyl, in another embodiment from the series
consisting of hydrogen and (C.sub.1-C.sub.3)-alkyl, in another
embodiment from the series consisting of hydrogen and
(C.sub.1-C.sub.2)-alkyl, in another embodiment from the series
consisting of hydrogen and methyl, and in another embodiment
R.sup.60 is hydrogen. In one embodiment of the invention, R.sup.50
and R.sup.60 both are hydrogen. In case R.sup.50 and R.sup.60 are
different and the carbon atom carrying R.sup.50 and R.sup.60 thus
is chiral, in one embodiment of the invention the compound of the
formula I has at this carbon atom pure stereochemical
configuration, either R configuration or S configuration, or
essentially pure stereochemical configuration, for example with a
molar ratio of the two configurations of 99:1 or greater.
[0058] In case R.sup.50 and R.sup.60 together are a divalent group
(CH.sub.2).sub.y, the two groups R.sup.50 and R.sup.60 together
with the carbon atom carrying them form a cycloalkane ring chosen
from cyclopropane, cyclobutane, cyclopentane and cyclohexane, which
carries the moieties --C(R.sup.30)(R.sup.40)-- and G depicted in
formula I on the same ring carbon atom. In one embodiment of the
invention, the number of (C.sub.1-C.sub.4)-alkyl substituents which
are optionally present on the group (CH.sub.2).sub.y, is one, two,
three or four, in another embodiment one or two, and in another
embodiment no alkyl substituents are present on the group
(CH.sub.2).sub.y. In one embodiment, a (C.sub.1-C.sub.4)-alkyl
group occurring as a substituent on the group (CH.sub.2).sub.y is a
methyl group. In one embodiment, the integer y is chosen from the
series consisting of 2, 4 and 5, in another embodiment from 4 and
5, in another embodiment y is 2, and in another embodiment y is 4.
In one embodiment of the invention, R.sup.50 and R.sup.60 together
cannot be (CH.sub.2).sub.y, and in this embodiment R.sup.50 and
R.sup.60 thus only have their other meanings as defined. In one
embodiment of the invention, R.sup.50 and R.sup.60 together cannot
be (CH.sub.2).sub.y if simultaneously R.sup.30 and R.sup.40
together are (CH.sub.2).
[0059] In one embodiment of the invention, the group R.sup.71 is
chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.6)-alkyl, in another embodiment from the series
consisting of hydrogen and (C.sub.1-C.sub.4)-alkyl, in another
embodiment from the series consisting of hydrogen and
(C.sub.1-C.sub.3)-alkyl, in another embodiment from the series
consisting of hydrogen and (C.sub.1-C.sub.2)-alkyl, in another
embodiment R.sup.71 is hydrogen, in another embodiment R.sup.71 is
(C.sub.1-C.sub.6)-alkyl, in another embodiment R.sup.71 is
(C.sub.1-C.sub.4)-alkyl, in another embodiment R.sup.71 is
(C.sub.1-C.sub.3)-alkyl, and in another embodiment R.sup.71 is
(C.sub.1-C.sub.2)-alkyl, wherein all these alkyl groups are
optionally substituted as indicated with respect to the compounds
of formula I in general or in any embodiment specified above or
below. In one embodiment, the number of substituents which are
optionally present on an alkyl group representing R.sup.71 is one
or two, in another embodiment it is one, in another embodiment an
alkyl group representing R.sup.71 is unsubstituted. In one
embodiment, substituents which are optionally present on an alkyl
group representing R.sup.71 are (C.sub.1-C.sub.6)-alkyl-O--
substituents, in another embodiment (C.sub.1-C.sub.4)-alkyl-O--
substituents, in another embodiment (C.sub.1-C.sub.3)-alkyl-O--
substituents, in another embodiment
(C.sub.1-C.sub.6)-alkyl-C(O)--O-- substituents, in another
embodiment (C.sub.1-C.sub.4)-alkyl-C(O)--O-- substituents, in
another embodiment (C.sub.1-C.sub.3)-alkyl-C(O)--O--
substituents.
[0060] In one embodiment the group R.sup.72 is chosen from the
series consisting of hydrogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.6)-cycloalkyl
--CH.sub.2--(CH.sub.2).sub.b--(C.sub.3-C.sub.6)-cycloalkyl and
--(CH.sub.2).sub.b-Het.sup.4, where alkyl or cycloalkyl is
optionally substituted by one or more identical or different
substituents chosen from the series consisting of halogen, HO--,
HOOC--, (C.sub.1-C.sub.6)-alkyl-O-- and
(C.sub.1-C.sub.6)-alkyl-C(O)--O--, NC--,
N((C.sub.1-C.sub.4)-alkyl).sub.2 and b is 0, 1 or 2 and the group
R.sup.73 is chosen from the series consisting hydrogen,
(C.sub.1-C.sub.6)-alkyl.
[0061] In another embodiment the groups R.sup.72 and R.sup.73
together with the nitrogen atom to which they are bonded form a
saturated 4-membered to 7-membered monocyclic heterocycle, which
contain optionally one further ring heteroatom chosen from the
series consisting of nitrogen, oxygen and sulfur, which is
optionally substituted by one or more identical or different
substituents chosen from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl, HO-- and (C.sub.1-C.sub.4)-alkyl-O--.
[0062] In another embodiment the group R.sup.72 is chosen from the
series consisting of hydrogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.6)-cycloalkyl, Het.sup.4 and --CH.sub.2-Het.sup.4,
where alkyl or cycloalkyl is optionally substituted by one or more
identical or different substituents chosen from the series
consisting of halogen, HO--, HOOC--, (C.sub.1-C.sub.6)-alkyl-O--
and (C.sub.1-C.sub.6)-alkyl-C(O)--O--, NC--,
N((C.sub.1-C.sub.4)-alkyl).sub.2 and the group R.sup.73 is chosen
from the series consisting hydrogen, (C.sub.1-C.sub.6)-alkyl.
[0063] In another embodiment the groups R.sup.72 and R.sup.73
together with the nitrogen atom to which they are bonded form a
saturated 5-membered to 6-membered monocyclic heterocycle, which
contain optionally one further ring heteroatom chosen from the
series consisting of nitrogen, oxygen and sulfur, which is
optionally substituted by one or more identical or different
substituents chosen from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl, HO-- and (C.sub.1-C.sub.4)-alkyl-O--.
[0064] In one embodiment the group R.sup.72 is chosen from the
series consisting of hydrogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.6)-cycloalkyl and --CH.sub.2-Het.sup.4, where alkyl
or cycloalkyl is optionally substituted by one or more identical or
different substituents chosen from the series consisting of
halogen, HO--, HOOC--, (C.sub.1-C.sub.6)-alkyl-O-- and
(C.sub.1-C.sub.6)-alkyl-C(O)--O--, NC--,
N((C.sub.1-C.sub.4)-alkyl).sub.2 and the group R.sup.73 is chosen
from the series consisting hydrogen and
(C.sub.1-C.sub.6)-alkyl.
[0065] In another embodiment the groups R.sup.72 and R.sup.73
together with the nitrogen atom to which they are bonded form a
saturated 5-membered to 6-membered monocyclic heterocycle, which
contain no further ring heteroatoms, which is optionally
substituted by one or more identical or different substituents
chosen from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl, HO-- and (C.sub.1-C.sub.4)-alkyl-O--.
[0066] In one embodiment the group R.sup.72 is chosen from the
series consisting of hydrogen, 2,2-dimethyl-butane-3yl,
2,2-dimethyl-propane-3yl, pentan-3yl, propane-2yl,
2-methyl-propane-2yl, butane-1yl, butane-2yl, 2-methyl-butane-3yl,
2-methyl-butane-2yl, --CH.sub.2CHF.sub.2, --CHCF.sub.3, CH.sub.2CN,
--CH.sub.2CH.sub.2OCH.sub.3, --CH(CH.sub.2OH)CH(CH.sub.3).sub.2,
--CH.sub.2C(CH.sub.3).sub.2--CH.sub.2OH,
CH(C.sub.2H.sub.5)CH.sub.2OCH.sub.3,
CH.sub.2CH.sub.2CH.sub.2N(CH.sub.3).sub.2, cyclopropane,
cyclobutane, cyclopentane, cyclohexane and --CH.sub.2-Het.sup.4 and
the group R.sup.73 is hydrogen.
[0067] In another embodiment the groups R.sup.72 and R.sup.73
together with the nitrogen atom to which they are bonded form
pyrrolidine, which is optionally substituted by HO--.
[0068] In another embodiment the group R.sup.72 is chosen from the
series consisting of hydrogen, (C.sub.1-C.sub.6)-alkyl, where alkyl
is substituted by one or more times by HO-- and the group R.sup.73
is hydrogen.
[0069] In one embodiment of the invention, the groups R.sup.72 and
R.sup.73 are independently of each other chosen from the series
consisting of hydrogen and (C.sub.1-C.sub.2)-alkyl, in another
embodiment from the series consisting of hydrogen and methyl. In
one embodiment, one of the groups R.sup.72 and R.sup.73 is hydrogen
and the other is chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.4)-alkyl, in another embodiment from the series
consisting of hydrogen and (C.sub.1-C.sub.2)-alkyl, in another
embodiment from the series consisting of hydrogen an methyl, and in
another embodiment both groups R.sup.72 and R.sup.73 are
hydrogen.
[0070] In one embodiment of the invention the group Het.sup.4,
independently of each other group Het.sup.4, is a saturated or
unsaturated 4-membered to 8-membered monocyclic heterocycle which
comprises one to four ring heteroatoms chosen from the series
consisting of nitrogen, oxygen and sulfur which is optionally
substituted by one or more identical or different substituents
chosen from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl, HO--, (C.sub.1-C.sub.4)-alkyl-O--, oxo and
NC--;
[0071] In another embodiment the group Het.sup.4, independently of
each other group Het.sup.4, is a saturated or unsaturated
5-membered to 6-membered monocyclic heterocycle which comprises one
to four ring heteroatoms chosen from the series consisting of
nitrogen, oxygen and sulfur which is optionally substituted by one
or more identical or different substituents chosen from the series
consisting of halogen, (C.sub.1-C.sub.4)-alkyl, HO--,
(C.sub.1-C.sub.4)-alkyl-O--, oxo and NC--;
[0072] In another embodiment the group Het.sup.4, independently of
each other group Het.sup.4, is a unsaturated 5-membered to
6-membered monocyclic heterocycle which comprises one to four ring
heteroatoms chosen from the series consisting of nitrogen, oxygen
and sulfur which is optionally substituted by one or more identical
or different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, HO--, (C.sub.1-C.sub.4)-alkyl-O--
and NC--;
[0073] In another embodiment the group Het.sup.4, independently of
each other group Het.sup.4, is selected from 1,2-oxadiazolyl,
tetrazlolyl, pyrazolyl, furanyl, pyridinyl, pyriminyl, which is
optionally substituted by methyl.
[0074] In one embodiment of the invention, a group Ar in any
occurrence in the compounds of the formula I, independently of each
other group Ar, is chosen from the series consisting of phenyl and
an aromatic 5-membered or 6-membered monocyclic heterocycle which
comprises one or two identical or different ring heteroatoms, in
another embodiment one ring heteroatom, which is chosen from the
series consisting of nitrogen, oxygen and sulfur, and which is
bonded via a ring carbon atom, in another embodiment Ar is chosen
from the series consisting of phenyl and an aromatic 6-membered
heterocycle which comprises one or two nitrogen atoms as ring
heteroatoms, in another embodiment Ar is chosen from the series
consisting of phenyl, thiophenyl and pyridinyl, in another
embodiment from the series consisting of phenyl and thiophenyl, in
another embodiment from the series consisting of phenyl and
pyridinyl, in another embodiment a group Ar is phenyl, and in
another embodiment a group Ar is pyridinyl, wherein the phenyl and
all heterocycles are optionally substituted as indicated with
respect to the compounds of formula I in general or in any
embodiment specified above or below. In one embodiment, the number
of substituents which are optionally present on a group Ar,
independently of each other group Ar, is one, two, three or four,
in another embodiment one, two or three, in another embodiment one
or two, in another embodiment one, and in another embodiment a
group Ar is unsubstituted. In one embodiment, in case that
substituents from the series consisting of --O--CH.sub.2--O-- and
--O--CF.sub.2--O-- are present on a group Ar, not more than two
such substituents, in another embodiment not more than one such
substituent, are present, either without any other substituents or
together with any other substituents. In one embodiment, the
substituents which are optionally present on a group Ar,
independently of each other group Ar, are chosen from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.1-C.sub.6)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m-- and NC--,
in another embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m-- and NC--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O-- and NC--, in
another embodiment from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl and (C.sub.1-C.sub.6)-alkyl-O--, in another
embodiment from the series consisting of halogen,
(C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkyl-O--, in another
embodiment from the series consisting of halogen and
(C.sub.1-C.sub.4)-alkyl.
[0075] A subject of the invention are all compounds of the formula
I wherein any one or more structural elements such as groups,
substituents and numbers are defined as in any of the specified
embodiments or definitions of the elements or have one or more of
the specific meanings which are mentioned herein as examples of
elements, wherein all combinations of one or more specified
embodiments and/or definitions and/or specific meanings of the
elements are a subject of the present invention. Also with respect
to all such compounds of the formula I, all their stereoisomeric
forms and mixtures of stereoisomeric forms in any ratios, and their
physiologically acceptable salts, and the physiologically
acceptable solvates of any of them, are a subject of the present
invention.
[0076] As an example of compounds of the invention which with
respect to any structural elements are defined as in specified
embodiments of the invention or definitions of such elements,
compounds of the formula I may be mentioned wherein
A is chosen from the series consisting of C(R.sup.1) and N; D is
chosen from the series consisting of N(R.sup.2), O and S;
E is N;
[0077] R.sup.1 is chosen from the series consisting of hydrogen,
halogen and (C.sub.1-C.sub.4)-alkyl; R.sup.2 is chosen from the
series consisting of (C.sub.3-C.sub.7)-cycloalkyl-C.sub.sH.sub.2s--
and Ar--C.sub.sH.sub.2s--, wherein s is an integer chosen from the
series consisting of 0, 1 and 2; and all other groups and numbers
are defined as in the general definition of the compounds of the
formula I or in any specified embodiments of the invention or
definitions of structural elements, in any of their stereoisomeric
forms or a mixture of stereoisomeric forms in any ratio, and their
physiologically acceptable salts, and the physiologically
acceptable solvates of any of them.
[0078] As another such example, compounds of the formula I may be
mentioned, wherein
A is chosen from the series consisting of C(R.sup.1) and N;
D is N(R.sup.2);
E is N;
[0079] R.sup.1 is chosen from the series consisting of hydrogen,
halogen and (C.sub.1-C.sub.4)-alkyl; R.sup.2 is
Ar--C.sub.sH.sub.2s--, wherein s is an integer chosen from the
series consisting of 0, 1 and 2; and all other groups and numbers
are defined as in the general definition of the compounds of the
formula I or in any specified embodiments of the invention or
definitions of structural elements, in any of their stereoisomeric
forms or a mixture of stereoisomeric forms in any ratio, and their
physiologically acceptable salts, and the physiologically
acceptable solvates of any of them.
[0080] As another such example, compounds of the formula I may be
mentioned, wherein
A is C(R.sup.1);
D is N(R.sup.2);
E is N;
[0081] R.sup.1 is chosen from the series consisting of hydrogen,
halogen and (C.sub.1-C.sub.4)-alkyl; R.sup.2 is
Ar--C.sub.sH.sub.2s--, wherein s is 0; the group Ar in the group
R.sup.2, irrespective of the meaning of Ar in other positions in
the compounds of the formula I, is chosen from the series
consisting of phenyl and an aromatic 6-membered heterocycle which
comprises one or two nitrogen atoms as ring heteroatoms, wherein
the phenyl and the heterocycle are all optionally substituted by
one, two or three identical or different substituents chosen from
the series consisting of halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.1-C.sub.6)-alkyl-O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--
and NC--; and all other groups and numbers are defined as in the
general definition of the compounds of the formula I or in any
specified embodiments of the invention or definitions of structural
elements, in any of their stereoisomeric forms or a mixture of
stereoisomeric forms in any ratio, and their physiologically
acceptable salts, and the physiologically acceptable solvates of
any of them.
[0082] As another such example, compounds of the formula I may be
mentioned, wherein
R.sup.10 is R.sup.11--O--;
[0083] R.sup.11 is chosen from the series consisting of hydrogen
and R.sup.14; R.sup.14 is (C.sub.1-C.sub.8)-alkyl which is
optionally substituted by one, two or three identical or different
substituents chosen from the series consisting of HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl, Ar, Het.sup.1 and
Het.sup.3; R.sup.16 is (C.sub.1-C.sub.6)-alkyl which is optionally
substituted by one or two identical or different substituents
chosen from the series consisting of HO-- and
(C.sub.1-C.sub.4)-alkyl-O--; and all other groups and numbers are
defined as in the general definition of the compounds of the
formula I or in any specified embodiments of the invention or
definitions of structural elements, in any of their stereoisomeric
forms or a mixture of stereoisomeric forms in any ratio, and their
physiologically acceptable salts, and the physiologically
acceptable solvates of any of them.
[0084] As another such example, compounds of the formula I may be
mentioned, wherein
G is chosen from the series consisting of R.sup.71--O--C(O)-- and
R.sup.72--N(R.sup.73)--C(O)--; R.sup.30 is
R.sup.32--C.sub.uH.sub.2u--, wherein u is an integer chosen from
the series consisting of 0 and 1; R.sup.32 is chosen from the
series consisting of phenyl and an aromatic 6-membered monocyclic
heterocycle which comprises one or two nitrogen atoms as ring
heteroatoms, wherein the phenyl and the heterocycle all are
optionally substituted by one, two or three identical or different
substituents chosen from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
(C.sub.1-C.sub.6)-alkyl-NH--, di((C.sub.1-C.sub.6)-alkyl)N--,
Het.sup.1 and NC--; R.sup.33 is chosen from the series consisting
of phenyl and pyridinyl which all are optionally substituted by
one, two or three identical or different substituents chosen from
the series consisting of halogen, (C.sub.1-C.sub.4)-alkyl,
(C.sub.1-C.sub.4)-alkyl-O--, (C.sub.1-C.sub.4)-alkyl-S(O).sub.m--
and NC--; R.sup.40 is hydrogen; R.sup.50 is hydrogen; R.sup.60 is
hydrogen; and all other groups and numbers are defined as in the
general definition of the compounds of the formula I or in any
specified embodiments of the invention or definitions of structural
elements, in any of their stereoisomeric forms or a mixture of
stereoisomeric forms in any ratio, and their physiologically
acceptable salts, and the physiologically acceptable solvates of
any of them.
[0085] As another such example, compounds of the formula I may be
mentioned, wherein
A is chosen from the series consisting of C(R.sup.1) and N;
D is N(R.sup.2);
[0086] E is chosen from the series consisting of C(R.sup.3) and N;
G is chosen from the series consisting of R.sup.71--O--C(O)-- and
R.sup.72--N(R.sup.73)--C(O)--; R.sup.1 is chosen from the series
consisting of hydrogen, halogen, (C.sub.1-C.sub.6)-alkyl, HO-- and
(C.sub.1-C.sub.6)-alkyl-O--; R.sup.2 is chosen from the series
consisting of (C.sub.1-C.sub.7)-alkyl,
(C.sub.3-C.sub.7)-cycloalkyl-C.sub.sH.sub.2s-- and
Ar--C.sub.sH.sub.2s--, wherein s is an integer chosen from the
series consisting of 0, 1, 2 and 3; R.sup.3 is chosen from the
series consisting of hydrogen, halogen, (C.sub.1-C.sub.6)-alkyl and
(C.sub.1-C.sub.6)-alkyl-O--; R.sup.10 is chosen from the series
consisting of R.sup.11--O--, R.sup.12--N(R.sup.13)--C(O)--O-- and
Het.sup.2-C(O)--O--; R.sup.11 is chosen from the series consisting
of hydrogen, R.sup.14, (C.sub.3-C.sub.7)-cycloalkyl and Het.sup.3;
R.sup.12 and R.sup.13 are independently of each other chosen from
the series consisting of hydrogen, R.sup.15 and Ar; R.sup.14 is
(C.sub.1-C.sub.10)-alkyl which is optionally substituted by one or
more identical or different substituents chosen from the series
consisting of halogen, HO--, R.sup.16--O--, oxo,
(C.sub.3-C.sub.7)-cycloalkyl, Ar, Het.sup.1, Het.sup.3, NC--,
H.sub.2N--C(O)--, (C.sub.1-C.sub.4)-alkyl-NH--C(O)--,
di((C.sub.1-C.sub.4)-alkyl)N--C(O)-- and Het.sup.1-C(O)--; R.sup.15
is (C.sub.1-C.sub.6)-alkyl; R.sup.16 is (C.sub.1-C.sub.6)-alkyl
which is optionally substituted by one or more identical or
different substituents chosen from the series consisting of HO--
and (C.sub.1-C.sub.4)-alkyl-O--; R.sup.30 is chosen from the series
consisting of (C.sub.3-C.sub.7)-cycloalkyl,
R.sup.32--C.sub.uH.sub.2u-- and Het.sup.3-C.sub.uH.sub.2u--,
wherein u is an integer chosen from the series consisting of 0, 1,
2 and 3; R.sup.32 is chosen from the series consisting of phenyl
and an aromatic 6-membered monocyclic heterocycle which comprises
one or two nitrogen atoms as ring heteroatoms, wherein the phenyl
and the heterocycle all are optionally substituted by one or more
identical or different substituents chosen from the series
consisting of halogen, (C.sub.1-C.sub.6)-alkyl,
(C.sub.3-C.sub.7)-cycloalkyl, R.sup.33, HO--,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2--, H.sub.2N--,
di((C.sub.1-C.sub.6)-alkyl)N--, Het.sup.1,
(C.sub.1-C.sub.4)-alkyl-C(O)--NH--, Ar--C(O)--NH-- and NC--;
R.sup.33 is chosen from the series consisting of phenyl and an
aromatic 6-membered monocyclic heterocycle which comprises one or
two nitrogen atoms as ring heteroatoms, wherein the phenyl and the
heterocycle all are optionally substituted by one or more identical
or different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-cycloalkyl,
HO--, (C.sub.1-C.sub.6)-alkyl-O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m--, H.sub.2N--S(O).sub.2--,
di((C.sub.1-C.sub.4)-alkyl)N--S(O).sub.2-- and NC--; R.sup.40 is
hydrogen; R.sup.50 is chosen from the series consisting of hydrogen
and HO--; R.sup.60 is hydrogen; R.sup.71 is chosen from the series
consisting of hydrogen and (C.sub.1-C.sub.8)-alkyl which is
optionally substituted by one or more identical or different
substituents chosen from the series consisting
(C.sub.1-C.sub.6)-alkyl-O-- and (C.sub.1-C.sub.6)-alkyl-C(O)--O--;
R.sup.72 and R.sup.73 are independently of each other chosen from
the series consisting of hydrogen and (C.sub.1-C.sub.4)-alkyl; Ar,
independently of each other group Ar, is chosen from the series
consisting of phenyl and an aromatic 5-membered or 6-membered
monocyclic heterocycle which comprises one, two or three identical
or different ring heteroatoms chosen from the series consisting of
nitrogen, oxygen and sulfur and is bonded via a ring carbon atom,
wherein the phenyl and the heterocycle all are optionally
substituted by one or more identical or different substituents
chosen from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O--,
--O--CH.sub.2--O--, --O--CF.sub.2--O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m-- and NC--; Het.sup.1,
independently of each other group Het.sup.1, is a saturated or
unsaturated 4-membered to 8-membered monocyclic heterocycle which
comprises a ring nitrogen atom via which Het.sup.1 is bonded and
optionally one or two identical or different further ring
heteroatoms chosen from the series consisting of nitrogen, oxygen
and sulfur, which is optionally substituted by one or more
identical or different substituents chosen from the series
consisting of halogen, (C.sub.1-C.sub.4)-alkyl, HO--,
(C.sub.1-C.sub.4)-alkyl-O--, oxo and NC--; Het.sup.2 is a saturated
4-membered to 7-membered monocyclic heterocycle which comprises a
ring nitrogen atom via which Het.sup.2 is bonded and optionally one
further ring heteroatom chosen from the series consisting of
nitrogen, oxygen and sulfur, which is optionally substituted by one
or more identical or different substituents chosen from the series
consisting of halogen, (C.sub.1-C.sub.4)-alkyl, HO-- and
(C.sub.1-C.sub.4)-alkyl-O--; Het.sup.3, independently of each other
group Het.sup.3, is a saturated 4-membered to 7-membered monocyclic
heterocycle which comprises one or two identical or different ring
heteroatoms chosen from the series consisting of nitrogen, oxygen
and sulfur and is bonded via a ring carbon atom, which is
optionally substituted by one or more identical or different
substituents chosen from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl and oxo; m, independently of each other
number m, is an integer chosen from the series consisting of 0, 1
and 2; wherein all cycloalkyl groups, independently of each other,
are optionally substituted by one or more identical or different
substituents chosen from the series consisting of fluorine and
(C.sub.1-C.sub.4)-alkyl; wherein all alkyl, C.sub.sH.sub.2s,
C.sub.uH.sub.2u, (CH.sub.2).sub.x and (CH.sub.2).sub.y groups,
independently of each other, and independently of any other
substituents, are optionally substituted by one or more fluorine
substituents; in any of their stereoisomeric forms or a mixture of
stereoisomeric forms in any ratio, and their physiologically
acceptable salts, and the physiologically acceptable solvates of
any of them.
[0087] As another such example, compounds of the formula I may be
mentioned, wherein
A is C(R.sup.1);
D is N(R.sup.2);
E is N;
[0088] G is chosen from the series consisting of
R.sup.71--O--C(O)-- and R.sup.72--N(R.sup.73)--C(O)--; R.sup.1 is
chosen from the series consisting of hydrogen, halogen and
(C.sub.1-C.sub.4)-alkyl; R.sup.2 is Ar--C.sub.sH.sub.2s--, wherein
s is 0;
R.sup.10 is R.sup.11--O--;
[0089] R.sup.11 is chosen from the series consisting of hydrogen
and R.sup.14; R.sup.14 is (C.sub.1-C.sub.10)-alkyl which is
optionally substituted by one, two or three identical or different
substituents chosen from the series consisting of HO--,
R.sup.16--O--, oxo, (C.sub.3-C.sub.7)-cycloalkyl, Ar, Het.sup.1,
di((C.sub.1-C.sub.4)-alkyl)N-- and Het.sup.1-C(O)--; R.sup.16 is
(C.sub.1-C.sub.6)-alkyl which is optionally substituted by one or
two identical or different substituents chosen from the series
consisting of HO-- and (C.sub.1-C.sub.4)-alkyl-O--; R.sup.30 is
R.sup.32--C.sub.uH.sub.2u--, wherein u is an integer chosen from
the series consisting of 0 and 1; R.sup.32 is chosen from the
series consisting of phenyl and an aromatic 6-membered monocyclic
heterocycle which comprises one or two nitrogen atoms as ring
heteroatoms, wherein the phenyl and the heterocycle all are
optionally substituted by one, two or three identical or different
substituents chosen from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.7)-Cycloalkyl, R.sup.33,
(C.sub.1-C.sub.6)-alkyl-O--, R.sup.33--O--,
R.sup.33--(C.sub.1-C.sub.4)-alkyl-O--, --O--CH.sub.2--O--,
--O--CF.sub.2--O--, (C.sub.1-C.sub.6)-alkyl-S(O).sub.m--,
di((C.sub.1-C.sub.6)-alkyl)N--, Het.sup.1 and NC--; R.sup.33 is
chosen from the series consisting of phenyl and pyridinyl which all
are optionally substituted by one, two or three identical or
different substituents chosen from the series consisting of
halogen, (C.sub.1-C.sub.4)-alkyl, (C.sub.1-C.sub.4)-alkyl-O--,
(C.sub.1-C.sub.4)-alkyl-S(O).sub.m-- and NC--; R.sup.40 is
hydrogen; R.sup.50 is hydrogen; R.sup.60 is hydrogen; R.sup.71 is
chosen from the series consisting of hydrogen and
(C.sub.1-C.sub.8)-alkyl which is optionally substituted by one
substituent chosen from the series consisting
(C.sub.1-C.sub.6)-alkyl-O-- and (C.sub.1-C.sub.6)-alkyl-C(O)--O--;
R.sup.72 and R.sup.73 are independently of each other chosen from
the series consisting of hydrogen and (C.sub.1-C.sub.2)-alkyl; Ar
is chosen from the series consisting of phenyl and an aromatic
6-membered heterocycle which comprises one or two nitrogen atoms as
ring heteroatoms, wherein the phenyl and the heterocycle are all
optionally substituted by one, two or three identical or different
substituents chosen from the series consisting of halogen,
(C.sub.1-C.sub.6)-alkyl, (C.sub.1-C.sub.6)-alkyl-O--,
(C.sub.1-C.sub.6)-alkyl-S(O).sub.m-- and NC--; Het.sup.1,
independently of each other group Het.sup.1, is a saturated or
unsaturated 4-membered to 6-membered monocyclic heterocycle which
comprises a ring nitrogen atom via which Het.sup.1 is bonded and
optionally one further ring heteroatom chosen from the series
consisting of nitrogen, oxygen and sulfur, which is optionally
substituted by one, two or three identical or different
substituents chosen from the series consisting of fluorine,
(C.sub.1-C.sub.4)-alkyl, HO-- and oxo; m, independently of each
other number m, is an integer chosen from the series consisting of
0, 1 and 2; wherein all cycloalkyl groups, independently of each
other, are optionally substituted by one or more identical or
different substituents chosen from the series consisting of
fluorine and (C.sub.1-C.sub.4)-alkyl; wherein all alkyl,
C.sub.sH.sub.2s and C.sub.uH.sub.2u groups, independently of each
other, and independently of any other substituents, are optionally
substituted by one or more fluorine substituents; in any of their
stereoisomeric forms or a mixture of stereoisomeric forms in any
ratio, and their physiologically acceptable salts, and the
physiologically acceptable solvates of any of them.
[0090] A subject of the invention also is a compound of the formula
I which is chosen from any of the specific compounds of the formula
I which are disclosed herein, or is any one of the specific
compounds of the formula I which are disclosed herein, irrespective
thereof whether they are disclosed as a free compound and/or as a
specific salt, or a physiologically acceptable salt thereof, or a
physiologically acceptable solvate of any of them, wherein the
compound of the formula I is a subject of the invention in any of
its stereoisomeric forms or a mixture of stereoisomeric forms in
any ratio. For example, a subject of the invention is a compound of
the formula I which is chosen from [0091]
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-methoxy-phenyl-
)-propionic acid, [0092]
3-(3-tert-Butoxy-phenyl)-3-{[1-(2,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazol-
e-3-carbonyl]-amino}-propionic acid, [0093]
(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o--
tolyl-propionic acid, [0094]
3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-pyrazol-
e-3-carbonyl]-amino}-propionic acid, [0095]
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-pyrazol-
e-3-carbonyl]-amino}-propionic acid, [0096]
(S)-3-[(5-Methoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propi-
onic acid, [0097]
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(2-methoxy-5-trif-
luoromethyl-phenyl)-propionic acid, [0098]
3-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3-carbony-
l)-amino]-propionic acid, [0099]
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(2'-fl-
uoro-biphenyl-4-yl)-propionic acid, [0100]
3-[(5-Methoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-pyridin-2-yl-p-
henyl)-propionic acid, [0101]
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(4-met-
hanesulfonyl-phenyl)-propionic acid, [0102]
(S)-3-{[5-Hydroxy-1-(2-methanesulfonyl-phenyl)-1H)-pyrazole-3-carbonyl]-a-
mino}-3-O-- tolyl-propionic acid, [0103]
3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(4-met-
hoxy-2-methyl-phenyl)-propionic acid, [0104]
(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-
-trifluoromethyl-phenyl)-propionic acid, [0105]
3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-c-
arbonyl]-amino}-propionic acid, [0106]
3-{[5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amin-
o}-3-(3-fluoro-2-methyl-phenyl)-propionic acid, [0107]
(S)-3-{[5-Cyclopropyl
methoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-prop-
ionic acid, [0108]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0109]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0110]
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-c-
arbonyl]-amino}-3-o-tolyl-propionic acid, [0111]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-
-propoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0112]
(S)-3-{[5-(2-Cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazo-
le-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0113]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-timethyl-butoxy)-1H-py-
razole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0114]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-timethyl-butoxy)-1H-py-
razole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0115]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0116]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0117]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro--
phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0118]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0119]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0120]
(S)-3-(2,5-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0121]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0122]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0123]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0124]
(S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0125]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionic
acid, [0126]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic acid,
[0127]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(4-methanesulfonyl-phenyl)-propionic
acid, [0128]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3-
,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0129]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-phenyl-propionic acid, [0130]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic
acid, [0131]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic
acid, [0132]
(S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-o-tolyl-propionic acid, [0133]
(S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-p-tolyl-propionic acid, [0134]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0135]
(S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-phenyl-propionic acid, [0136]
(S)-3-(2-Chloro-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-pheny-
l-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0137]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0138]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0139]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0140]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0141]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0142]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0143]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0144]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0145]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((R)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0146]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2,3-dichloro-phenyl)-propionic acid,
[0147]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2,4-dichloro-phenyl)-propionic acid,
[0148]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-phenyl-propionic acid, [0149]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-phenyl-propionic acid, [0150]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0151]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0152]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0153]
(S)-3-(2,5-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0154]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0155]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0156]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0157]
(S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0158]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionic
acid, [0159]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic acid,
[0160]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(4-methanesulfonyl-phenyl)-propionic
acid, [0161]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3-
,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0162]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-phenyl-propionic acid, [0163]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic
acid, [0164]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic
acid, [0165]
(S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-o-tolyl-propionic acid, [0166]
(S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-p-tolyl-propionic acid, [0167]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0168]
(S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-phenyl-propionic acid, [0169]
(S)-3-(2-Chloro-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-pheny-
l-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0170]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0171]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0172]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0173]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0174]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0175]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0176]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0177]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0178]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((S)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0179]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2,3-dichloro-phenyl)-propionic acid,
[0180]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2,4-dichloro-phenyl)-propionic acid,
[0181]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-phenyl-propionic acid, [0182]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-phenyl-propionic acid, [0183]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0184]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0185]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0186]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0187]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0188]
(S)-3-{[5-((R)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-c-
arbonyl]-amino}-3-o-tolyl-propionic acid, [0189]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0190]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0191]
(S)-3-{[5-((R)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-c-
arbonyl]-amino}-3-m-tolyl-propionic acid, [0192]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0193]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0194]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0195]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0196]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0197]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0198]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0199]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic
acid,
[0200]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-b-
utoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0201]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0202]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0203]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0204]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(2,4-dimethyl-phenyl)-propionic acid,
[0205]
(S)-3-(2-Chloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-ph-
enyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0206]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0207]
(S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0208]
(S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0209]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0210]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0211]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0212]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0213]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0214]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0215]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0216]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0217]
(S)-3-(2,5-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0218]
(S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0219]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0220]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0221]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0222]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0223]
(S)-3-{[5-((S)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-c-
arbonyl]-amino}-3-o-tolyl-propionic acid, [0224]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0225]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0226]
(S)-3-{[5-((S)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-c-
arbonyl]-amino}-3-m-tolyl-propionic acid, [0227]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0228]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0229]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0230]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0231]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0232]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0233]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0234]
(S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0235]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0236]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0237]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0238]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0239]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(2,4-dimethyl-phenyl)-propionic acid,
[0240]
(S)-3-(2-Chloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-ph-
enyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0241]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0242]
(S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0243]
(S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0244]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0245]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0246]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0247]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0248]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0249]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0250]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0251]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0252]
(S)-3-(2,5-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)--
1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0253]
(S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0254]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0255]
(S)-3-{[5-((R)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-o-tolyl-propionic acid, [0256]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0257]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0258]
(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0259]
(S)-3-{[5-((R)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-phenyl-propionic acid, [0260]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0261]
(S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0262]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0263]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0264]
S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-d-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0265]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0266]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3--
d methyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0267]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0268]
(S)-3-{[5-((R)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-p-tolyl-propionic acid, [0269]
S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1-ph-
enyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0270]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0271]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0272]
(S)-3-{[5-((S)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-o-tolyl-propionic acid, [0273]
(S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0274]
(S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0275]
(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0276]
(S)-3-{[5-((S)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-phenyl-propionic acid, [0277]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0278]
(S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0279]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0280]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0281]
S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-d-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0282]
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1-p-
henyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0283]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3--
d methyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0284]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0285]
(S)-3-{[5-((S)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carb-
onyl]-amino}-3-p-tolyl-propionic acid, [0286]
S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1-ph-
enyl-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0287]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0288]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0289]
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0290]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0291]
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-but-
oxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0292]
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0293]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-
-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0294]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0295]
(S)-3-(2-Chloro-phenyl)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phe-
nyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0296]
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tri-
methyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0297]
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0298]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0299]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0300]
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-
-butoxy)-1H-pyrazoie-3-carbonyl]-amino}-propionic acid, [0301]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic acid, [0302]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic
acid, [0303]
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-d-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0304]
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy-
)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0305]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-p-tolyl-propionic acid [0306]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0307]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0308]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0309]
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-c-
arbonyl]-amino}-3-p-tolyl-propionic acid,
[0310]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0311]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0312]
(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0313]
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0314]
(S)-3-(3-Chloro-phenyl)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phe-
nyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0315]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0316]
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0317]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic
acid, [0318]
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydro-
xy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic
acid, [0319]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0320]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic acid, [0321]
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy-
)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0322]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-m-tolyl-propionic acid, [0323]
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-c-
arbonyl]-amino}-3-m-tolyl-propionic acid, [0324]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic acid, [0325]
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl--
butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0326]
(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0327]
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0328]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic acid,
[0329]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic acid, [0330]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic acid,
[0331]
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-
-pyrazole-3-carbonyl]-amino}-propionic acid, [0332]
3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-c-
arbonyl]-amino}-5-methyl-hexanoic acid, [0333]
(R)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-3,3-dimethyl-
-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0334]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0335]
(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0336]
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyraz-
ole-3-carbonyl]-amino}-4-phenyl-butyric acid, [0337]
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0338]
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-but-
oxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0339]
3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-4-phenyl-butyric acid, [0340]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic acid, [0341]
3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0342]
(1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazol-
e-3-carbonyl]-amino}-cyclopentyl)-acetic acid, [0343]
(1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazol-
e-3-carbonyl]-amino}-cyclopentyl)-acetic acid, [0344]
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-4-phenyl-butyric acid, [0345]
3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-2-phenyl-propionic acid, [0346]
(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0347]
3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-c-
arbonyl]-amino}-4-phenyl-butyric acid, [0348]
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-2-phenyl-propionic acid, [0349]
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tri-
methyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric acid, [0350]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0351]
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimet-
hyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric acid, [0352]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0353]
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl--
butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric acid, [0354]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-4-phenyl-butyric acid, [0355]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-4-phenyl-butyric acid, [0356]
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-
-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0357]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic acid, [0358]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0359]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0360]
(1-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3--
carbonyl]-amino}-cyclopentyl)-acetic acid, [0361]
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-
-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0362]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0363]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-
-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0364]
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dim-
ethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0365]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic acid, [0366]
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3--
d methyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0367]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic acid, [0368]
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyraz-
ole-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0369]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-4-phenyl-butyric acid, [0370]
(1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-cyclopentyl)-acetic acid, [0371]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0372]
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-
,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0373]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic acid,
[0374]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0375]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0376]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0377]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-p-tolyl-propionic acid, [0378]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0379]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0380]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic
acid, [0381]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)--
1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric acid, [0382]
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimet-
hyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0383]
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-
-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0384]
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimet-
hyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric acid, [0385]
(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3--
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0386]
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0387]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-o-tolyl-propionic acid, [0388]
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0389]
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0390]
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0391]
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimet-
hyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0392]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic acid, [0393]
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0394]
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dime-
thyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid, [0395]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0396]
(1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyra-
zole-3-carbonyl]-amino}-cyclopentyl)-acetic acid, [0397]
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0398]
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,-
3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0399]
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-tr-
imethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0400]
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-
,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
[0401]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic acid,
[0402]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-5-methyl-hexanoic acid, [0403]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic
acid, [0404]
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,-
3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric acid,
[0405]
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-p-
yrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic acid,
[0406]
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2-phenyl-propoxy)-1H-pyrazole-3--
carbonyl]-amino}-3-o-tolyl-propionic acid, [0407]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(pyridin-2-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide;
compound with trifluoro-acetic acid, [0408]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(cyclopropylmethyl-carbamoyl)-1-o-tolyl-ethyl]-amide, [0409]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(furan-2-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,
[0410] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(3-dimethylamino-propylcarbamoyl)-1-o-tolyl-ethyl]-amide;
[0411] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(1-ethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide, [0412]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-cyclohexylcarbamoyl-1-o-tolyl-ethyl)-amide, [0413]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-3-((S)-3-hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide,
[0414] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-1-o-tolyl-2-((R)-1,2,2-trimethyl-propylcarbamoyl)-ethyl]-amide,
[0415] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-3-((R)-3-hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide,
[0416] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-((S)-sec-butylcarbamoyl)-1-o-tolyl-ethyl]-amide, [0417]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-3-((S)-3-hydroxy-piperidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide,
[0418] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(carbamoylmethyl-methyl-carbamoyl)-1-o-tolyl-ethyl]-amide,
[0419] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-((R)-1-cyclopropyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0420] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-((S)-1-cyclopropyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0421] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-cyclobutylcarbamoyl-1-o-tolyl-ethyl)-amide, [0422]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(pyridin-3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide;
compound with trifluoro-acetic acid, [0423]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-cyclopentylcarbamoyl-1-o-tolyl-ethyl)-amide, [0424]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(2-methoxy-1-methyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0425] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(2,2-difluoro-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide, [0426]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-1-o-tolyl-2-(2,2,2-trifluoro-ethyl carbamoyl)-ethyl]-amide,
[0427] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(2-cyclopropyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0428] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(pyrimidin-5-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,
[0429] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-butylcarbamoyl-1-o-tolyl-ethyl)-amide, [0430]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(furan-3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,
[0431] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(pyridin-4-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide;
compound with trifluoro-acetic acid, [0432]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(1,1-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0433] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-((R)-sec-butylcarbamoyl)-1-o-tolyl-ethyl]-amide, [0434]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-isobutylcarbamoyl-1-o-tolyl-ethyl)-amide, [0435]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-1-o-tolyl-2-((S)-1,2,2-trimethyl-propylcarbamoyl)-ethyl]-amide,
[0436] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(1-methoxymethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0437] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-tert-butylcarbamoyl-1-o-tolyl-ethyl)-amide, [0438]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(5-methyl-1H-pyrazol-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0439] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(2,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0440] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(3-hydroxy-2,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0441] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(cyanomethyl-carbamoyl)-1-o-tolyl-ethyl]-amide, [0442]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-((R)-1-hydroxymethyl-2-methyl-propylcarbamoyl)-1-o-tolyl-ethyl]-am-
ide, [0443] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
{(S)-2-[(1H-tetrazol-5-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,
[0444] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-isopropylcarbamoyl-1-o-tolyl-ethyl)-amide, [0445]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0446] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(2-oxo-pyrrolidin-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0447] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(5-methyl-isoxazol-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0448] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-cyclopropylcarbamoyl-1-o-tolyl-ethyl)-amide, [0449]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
{(S)-2-[(isoxazol-5-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,
[0450] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(2-methoxy-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide, [0451]
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-((S)-1-hydroxymethyl-2-methyl-propylcarbamoyl)-1-o-tolyl-ethyl]-am-
ide, [0452] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
[(S)-2-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,
[0453] 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
((S)-2-{[(S)-1-(tetrahydro-furan-2-yl)methyl]-carbamoyl}-1-o-tolyl-ethyl)-
-amide and 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
[(S)-2-((R)-1,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,
or which is any one of these compounds, or a physiologically
acceptable salt thereof, or a physiologically acceptable solvate of
any of them, wherein the compound of the formula I is a subject of
the invention in any of its stereoisomeric forms or a mixture of
stereoisomeric forms in any ratio, unless a specific stereoisomeric
form is specified with respect to any carbon atoms in the
respective compound.
[0454] Another subject of the present invention are processes for
the preparation of the compounds of the formula I which are
outlined below and by which the compounds are obtainable. For
example, the preparation of the compounds of the formula I can be
carried out by reacting a compound of the formula II with a
compound of the formula III with formation of an amide bond.
Various synthetic methods for the formation of the amide bond are
described in C. A. G. N. Montalbetti et al., Tetrahedron 61 (2005),
10827-10852, for example.
##STR00010##
[0455] The groups A, D, E, G, R.sup.10, R.sup.30, R.sup.40,
R.sup.50 and R.sup.60 in the compounds of the formulae II and III
are defined as in the compounds of the formula I and additionally
functional groups can be present in protected form or in the form
of a precursor group which is later converted into the final group.
The group J in the compounds of the formula II can be HO--
(hydroxy), i.e. the compound of the formula II can thus be a
carboxylic acid, or another group which can be replaced by the
group NH in the compound of the formula III in a substitution
reaction, for example an aryloxy group such as optionally
substituted phenoxy or an alkyloxy group such as a
(C.sub.1-C.sub.4)-alkyl-O-- group, for example a
(C.sub.1-C.sub.3)-alkyl-O-- group like methoxy or ethoxy, or
halogen, for example chlorine or bromine, and the compound of the
formula II can thus be a reactive ester like an aryl ester or alkyl
ester, for example a methyl ester or ethyl ester, or an acid
halide, for example an acid chloride or acid bromide, of the
respective carboxylic acid. The compounds of the formulae II and
III can also be employed, and the compounds of the formula I
obtained, in the form of a salt, for example an acid addition salt
such as an hydrohalide, for example a hydrochloride, of the
compound of the formula III and/or an alkaline metal salt, for
example a sodium salt, of a compound of the formula II in which J
is HO--. Likewise, in all other reactions in the preparation of the
compounds of the formula I, including the preparation of starting
compounds, compounds can also be employed and/or products obtained
in the form a salt.
[0456] In case a compound of the formula II is employed in which J
is HO--, the carboxylic acid group HO--C(O)-- is generally
activated in situ by means of a customary amide coupling reagent or
converted into a reactive carboxylic acid derivative which can be
prepared in situ or isolated. For example, the compound of the
formula II in which J is HO-- can be converted into an acid halide,
such as the compound of the formula II in which J is chlorine or
bromine, by treatment with thionyl chloride, phosphorus
pentachloride, phosphorus tribromide or oxalyl chloride, or treated
with an alkyl chloroformate like ethyl chloroformate or isobutyl
chloroformate to give a mixed anhydride. In a favorable method for
the conversion into the acid chloride, the acid is treated with
oxalyl chloride in the presence of a catalytic amount of an amide
such as N,N-dimethylformamide in an inert solvent such as a
hydrocarbon or chlorinated hydrocarbon or an ether, at temperatures
from about 0.degree. C. to about 60.degree. C., for example at room
temperature. Customary amide coupling reagents which can be
employed, are propanephosphonic anhydride, N,N'-carbonyldiazoles
like N,N'-carbonyldiimidazole (CDI), carbodiimides like
1,3-diisopropylcarbodiimide (DIC), 1,3-dicyclohexylcarbodiimide
(DCC) or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
hydrochloride (EDC), carbodiimides together with additives like
1-hydroxy-benzotriazole (HOBT) or 1-hydroxy-7-azabenzotriazole
(HOAT), uronium-based coupling reagents like
O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate (HATU),
O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate (HBTU) or
O-(cyano(ethoxycarbonyl)methyleneamino)-N,N,N',N'-tetramethylur-
onium tetrafluoroborate (TOTU), and phosphonium-based coupling
reagents like (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium
hexafluorophosphate (BOP),
(benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate
(PyBOP) or bromotripyrrolidinophosphonium hexafluorophosphate
(PyBroP).
[0457] The reaction conditions for the preparation of the compounds
of the formula I from compounds of the formulae II and III depend
on the particulars of the specific case, for example the meaning of
the group J or the employed coupling reagent, and are familiar to a
skilled person in view of the general knowledge in the art. For
example, in case a compound of the formula II in which J is
alkyl-O--, like methoxy or ethoxy, is reacted with a compound of
the formula III, generally the reaction is carried out in an inert
solvent, for example a hydrocarbon or chlorinated hydrocarbon like
benzene, toluene, xylene, chlorobenzene, dichloromethane,
chloroform or dichloroethane, an ether like tetrahydrofuran (THF),
2-methyltetrahydrofuran, dioxane, dibutyl ether, diisopropyl ether
or dimethoxyethane (DME), or a mixture of solvents, at elevated
temperatures, for example at temperatures from about 40.degree. C.
to about 140.degree. C., in particular at temperatures from about
50.degree. C. to about 120.degree. C., for example at about the
boiling temperature of the solvent. In case a compound of the
formula II in which J is halogen, like chlorine or bromine, is
reacted with a compound of the formula III, generally the reaction
is likewise carried out in an inert solvent, for example a
hydrocarbon or chlorinated hydrocarbon or ether like the
aforementioned ones, an ester like ethyl acetate or butyl acetate,
a nitrile like acetonitrile, or water, or a mixture of solvents
including a mixture of water and an organic solvent which is
miscible or immiscible with water, at temperatures from about
-10.degree. C. to about 100.degree. C., in particular at
temperatures from about 0.degree. C. to about 80.degree. C., for
example at about room temperature. Favorably, the reaction of a
compound of the formula II in which J is halogen with a compound of
the formula III is carried out in the presence of a base such as a
tertiary amine, like triethylamine, N-ethyl-diisopropylamine
(EDIA), N-methylmorpholine, N-ethylmorpholine or pyridine, or an
inorganic base such as an alkaline metal hydroxide, carbonate or
hydrogencarbonate, like sodium hydroxide, potassium hydroxide,
sodium carbonate or sodium hydrogencarbonate.
[0458] In case a compound of the formula II in which J is HO-- is
reacted with a compound of the formula III and the carboxylic acid
group is activated by means of an amide coupling reagent such as,
for example, a carbodiimide or TOTU, the reaction is generally
carried out under anhydrous conditions in an inert aprotic solvent,
for example an ether like THF, dioxane or DME, an amide like
N,N-dimethylformamide (DMF) or N-methylpyrrolidone (NMP), at
temperatures from about -10.degree. C. to about 40.degree. C., in
particular at temperatures from about 0.degree. C. to about
30.degree. C., for example at room temperature, in the presence of
a base such as a tertiary amine, like triethylamine, EDIA,
N-methylmorpholine or N-ethylmorpholine. In case the compound of
the formula III is employed in the form of an acid addition salt in
the reaction with the compound of the formula II, usually a
sufficient amount of a base is added in order to liberate the free
compound of the formula III.
[0459] As indicated above, during the formation of the amide bond
between the compounds of the formulae II and III functional groups
in the compounds of the formulae II and III can be present in
protected form or in the form of a precursor group. Depending on
the particulars of the specific case, it may be necessary or
advisable for avoiding an undesired course of the reaction or side
reactions to temporarily block any functional groups by protective
groups and remove them later, or to let functional groups be
present in the form of a precursor group which is later converted
into the desired final group. This applies correspondingly to all
reactions in the course of the synthesis of the compounds of the
formula I including the synthesis of intermediates, starting
compounds and building blocks. Respective synthetic strategies are
commonly used in the art. Details about protective groups and their
introduction and removal are described in P. G. M. Wuts and T. W.
Greene, Greene's Protective Groups in Organic Synthesis, 4. ed.
(2007), John Wiley & Sons, for example. Examples of protective
groups which may be mentioned, are benzyl protective groups which
may occur in the form of benzyl ethers of hydroxy groups and benzyl
esters of carboxylic acid groups from which the benzyl group can be
removed by catalytic hydrogenation in the presence of a palladium
catalyst, tert-butyl protective groups which may occur in the form
of tert-butyl esters of carboxylic acid groups from which the
tert-butyl group can be removed by treatment with trifluoroacetic
acid, acyl protective groups which may be used to protect hydroxy
groups and amino groups in the form of esters and amides and which
can be cleaved by acidic or basic hydrolysis, and alkyloxycarbonyl
protective groups which may occur in the form of
tert-butoxycarbonyl derivatives of amino groups which can be
cleaved by treatment with trifluoroacetic acid. Undesired reactions
of carboxylic acid groups, for example the carboxylic acid group
present in the compound of the formula III in case G is a
carboxylic acid group in the desired compound of the formula I, can
also be avoided by employing them in the reaction with the
compounds of the formula II in the form of other esters, for
example in the form of alkyl esters like the methyl or ethyl ester
which can be cleaved by hydrolysis, for example by means of an
alkaline metal hydroxide like sodium hydroxide or lithium
hydroxide. As examples of a precursor group, the cyano group (NC--,
NEC--) may be mentioned which can be converted into a carboxylic
acid group, a carboxylic acid ester group and a carboxamide group
under hydrolytic conditions or into a aminomethyl group by
reduction, and the nitro group which can be converted into an amino
group by reduction, for example by catalytic hydrogenation or by
reduction with sodium dithionite, for example. A further example of
a precursor group is an oxo group, which may initially be present
in the course of the synthesis of compounds of the formula I
containing a hydroxy group, and which can be reduced, for example
with a complex hydride such as sodium borohydride, or reacted with
an organometallic compound, for example a Grignard compound. If any
protective groups or precursor groups are present in the compounds
of the formulae II and III and the direct product of the reaction
is not yet the desired final compound, the removal of the
protective group or conversion into the desired compound can in
general also be carried out in situ.
[0460] The starting compounds for the synthesis of the compounds of
the formula I can generally be prepared according to procedures
described in the literature or analogously to such procedures, or
are commercially available. As an example of the synthesis of
compounds of the formula II, synthetic procedures for the synthesis
of compounds of the formula II in which A is C(R.sup.1), D is
N(R.sup.2) and E is N, i.e. of 5-oxygen-substituted
pyrazole-3-carboxylic acids and acid derivatives, are outlined in
the following. In one such procedure, oxalacetic acid of the
formula IV is reacted with a substituted hydrazine of the formula V
in a solvent such as water in the presence of an acid, such as
sulfuric acid, hydrochloric acid or acetic acid, to give a
5-hydroxy-pyrazole-3-carboxylic acid of the formula IIa in which R
and R.sup.1 are hydrogen and which can then be reacted with a
compound of the formula III.
##STR00011##
[0461] In a similar manner can diethyl oxalacetate, i.e. the
compound of the formula VI in which R.sup.1 is hydrogen and R' is
ethyl, be reacted with a substituted hydrazine to give a compound
of the formula IIa in which R.sup.1 is hydrogen and R is ethyl, and
can substituted oxalylacetates, for example compounds of the
formula VI in which R.sup.1 is an alkyl group such as methyl or
ethyl and R' is ethyl, be reacted with a substituted hydrazine, for
example by heating the components and/or treating them with a base
such as an alkaline metal hydroxide like sodium hydroxide or
potassium hydroxide, to give a compound of the formula IIa in which
R.sup.1 is hydrogen or has another meaning than hydrogen,
respectively, and R is an alkyl group, as described in S. Sugiura
et al., J. Med. Chem. 20 (1997), 80-85; P. E. Gagnon et al., Can.
J. Chem. 30 (1952), 904-914; or JP 2000/169453, for example.
Compounds of the formula IIa, in which R.sup.1 is hydrogen and R is
an alkyl group such as methyl, can also be prepared by reaction of
an acetylenedicarboxylate of the formula VII, for example dimethyl
acetylenedicarboxylate, with a hydrazine derivative in a solvent
such as an alcohol like methanol in the presence of a base such as
a tertiary amine, for example triethylamine or EDIA (cf. E.
Buchner, Chem. Ber. 22 (1889), 2929-2932). The groups R.sup.1 and
R.sup.2 in the compounds of the formulae IIa, V and VI are defined
as in the compounds of the formula I and additionally functional
groups can be present in protected form or in the form of a
precursor group which is later converted into the final group.
Depending on the individual case, in these procedures R.sup.1 is in
particular hydrogen or a group such as (C.sub.1-C.sub.6)-alkyl, for
example methyl or ethyl, and R.sup.2 is in particular an aromatic
group such as an optionally substituted phenyl group or aromatic
heterocyclic group. The group R' in the compounds of the formulae
VI and VII is (C.sub.1-C.sub.4)-alkyl, for example methyl or ethyl.
As indicated, the group R in the compounds of the formula IIa can
be hydrogen or (C.sub.1-C.sub.4)-alkyl, for example methyl or
ethyl. The compounds of the formula IIa, as well as other suitable
compounds occurring in the synthesis of the compounds of the
formula I and the compounds of the formula I themselves, can also
be present in other tautomeric forms, in particular the form in
which the hydroxy group in 5-position is present as an oxo group
and the ring nitrogen atom in 2-position carries a hydrogen
atom.
[0462] If desired for the intended use of the compound of the
formula IIa in the synthesis of the compound of the formula I, a
compound of the formula IIa in which R is hydrogen, i.e. a
carboxylic acid, can easily be converted into a compound of the
formula IIa in which is R is (C.sub.1-C.sub.4)-alkyl, or into
another carboxylic acid ester, as well as a compound of the formula
IIa is (C.sub.1-C.sub.4)-alkyl can be converted into a compound of
the formula IIa in which R is hydrogen. Such conversions can be
performed under standard conditions which are well known to a
person skilled in the art. For example, an esterification of a
carboxylic acid to give an ester such as a methyl or ethyl ester
can be performed by treating the carboxylic acid in the respective
alcohol as solvent with an acid like hydrogen chloride or with
thionyl chloride, and a saponification of a carboxylic acid ester
such as a methyl or ethyl ester to give the carboxylic acid can be
performed by treating the ester in a solvent such as an alcohol
like methanol or ethanol, an ether like THF or dioxane, or a ketone
like methyl isobutyl ketone, or a mixture thereof in the presence
of water with a base such as an alkaline metal hydroxide like
sodium hydroxide or lithium hydroxide. This applies just so to
carboxylic acid groups and carboxylic acid ester groups in other
compounds occurring in the synthesis of the compounds of the
formula I.
[0463] Compounds of the formula IIa can readily be converted into
compounds of the formula IIb, which are substituted on the hydroxy
group in 5-position and which can likewise be reacted with a
compound of the formula III, by reaction with an electrophilic
reagent of the formula VIII.
##STR00012##
[0464] The groups R.sup.1, R.sup.2 and R in the compounds of the
formula IIb are defined as in the compounds of the formula lib. The
group R.sup.10a in the compounds of the formulae IIb and VIII is
chosen from the series consisting R.sup.11,
R.sup.12--N(R.sup.13)--C(O)-- and Het.sup.2-C(O)-- wherein
R.sup.11, R.sup.12. R.sup.13 and Het.sup.2 are defined as in the
compounds of the formula I, except that R.sup.11 is not hydrogen,
and additionally functional groups can be present in protected form
or in the form of a precursor group which is later converted into
the final group, i.e. the group R.sup.10--O-- is substantially
defined as the group R.sup.10 in the compounds of the formula I,
except that it is not a hydroxy group. The group L in the compounds
of the formula VIII is a nucleophilically substitutable leaving
group which can be replaced by the oxygen atom of the hydroxy group
in the compound of the formula IIa in the respective reaction type,
for example halogen such as fluorine, chlorine, bromine or iodine,
or a sulfonyloxy group such as methanesulfonyloxy,
trifluoromethanesulfonyloxy, toluenesulfonyloxy, methoxysulfonyloxy
or ethoxysulfonyloxy, or L can also be a hydroxy group and in the
latter case the compounds of the formulae IIa and VIII reacted
under the conditions of the Mitsunobu reaction, for example.
[0465] In case the group R.sup.10a is R.sup.12--N(R.sup.13)--C(O)--
or Het.sup.2-C(O)--, the group L in the respective compounds of the
formula VIII advantageously is chlorine and the compound of the
formula VIII thus is an acyclic or cyclic carbamyl chloride. The
reaction of such a compound of the formula VIII with a compound of
the formula IIa is generally carried out in an inert solvent, for
example a hydrocarbon or a chlorinated hydrocarbon like toluene,
dichloromethane or dichloroethane, an ether like THF or dioxane, in
the presence of a base such as an amine like triethylamine or EDIA,
or an inorganic base like a basic alkaline metal salt, for example
a carbonate like sodium carbonate or cesium carbonate, at
temperatures from about 0.degree. C. to about 80.degree. C., in
particular from about 20.degree. C. to about 60.degree. C.
[0466] In case the group R.sup.10a in the compound of the formula
VIII is R.sup.11, the group R.sup.11 is a group such as alkyl, for
example, the group L is halogen or a sulfonyloxy group and the
compound of the formula VIII thus is an alkyl halide, an alkyl
sulfonate or a dialkyl sulfate, or a respective compound of another
type, the reaction of the compounds of the formulae IIa and VIII is
an O-alkylation and constitutes a nucleophilic substitution
reaction. Suitable conditions for such a reaction are well known to
a person skilled in the art and have extensively been described in
the literature, for example in S. Sugiura et al., J. Med. Chem. 80
(1977), 80-85; W.-M. Liu et al., J. Heterocycl. Chem. 44 (2007),
967-971; or U.S. Pat. No. 5,258,397. Generally the reaction is
carried out in an inert solvent, for example a hydrocarbon or
chlorinated hydrocarbon such as benzene, toluene, chlorobenzene,
dichloromethane, chloroform or dichloroethane, an ether such as
THF, dioxane, dibutyl ether, diisopropyl ether or DME, an alcohol
such as methanol, ethanol or isopropanol, a ketone such as acetone,
butan-2-one or methyl isobutyl ketone, an ester such as ethyl
acetate or butyl acetate, a nitrile such acetonitrile, an amide
such as DMF or NMP, or a mixture of solvents, including two-phasic
mixtures with aqueous solutions, at temperatures from about
-20.degree. C. to about 100.degree. C., for example at temperatures
from about 0.degree. C. to about 80.degree. C., depending on the
particulars of the specific case. The reaction can also be carried
out in the presence of an ionic liquid. Generally it is favorable
for enhancing the nucleophilicity of the compound of the formula
IIa and/or binding an acid which is liberated during the reaction,
to add a base, for example a tertiary amine, such as triethylamine,
EDIA or N-methylmorpholine, or an inorganic base such as an
alkaline metal hydride, hydroxide, carbonate or hydrogencarbonate
like sodium hydride, sodium hydroxide, potassium hydroxide, sodium
carbonate, potassium carbonate, cesium carbonate or sodium
hydrogencarbonate, or an alkoxide or amide such as sodium
methoxide, sodium ethoxide, potassium methoxide, potassium
tert-butoxide, sodium amide or lithium diisopropylamide, wherein a
compound of the formula IIa can also be treated with a base
separately before the reaction with the compound of the formula
VIII. By the choice of the reaction conditions, such as the solvent
and the base, as well as the choice of the group L in the compound
of the formula VIII, which compound can in the case that R.sup.10a
is methyl be a halide such as iodomethane or bromomethane, a
sulfonate such as methyl tosylate, or a sulfate such as dimethyl
sulfate, for example, it is also possible to control the
regioselectivity of the reaction with the compound of the formula
IIa which reaction can, besides on the oxygen atom of the hydroxy
group in 5-position, also occur on the ring nitrogen atom in
2-position, as is known to a person skilled in the art. If a
compound of the formula IIa in which R is hydrogen, is reacted with
a compound of the formula VIII in which R.sup.10a is R.sup.11,
besides on the hydroxy group in 5-position can a reaction with the
compound of the formula VIII also occur on the carboxylic acid
group, and the latter can be converted into an ester. For the
subsequent reaction step, such an ester group can be converted in
the carboxylic acid, as outlined above.
[0467] In case the group R.sup.10a in the compound of the formula
VIII is R.sup.11, the group R.sup.11 is a group such as alkyl, for
example, the group L is hydroxy and the compound of the formula
VIII thus is an alkanol, or a respective compound of another type,
the reaction of the compounds of the formulae IIa and VIII can be
performed under the conditions of the Mitsunobu reaction, as
mentioned above. The Mitsunobu reaction is generally performed in
an inert solvent, such as a hydrocarbon or chlorinated hydrocarbon
like toluene or dichloromethane, or an ether like THF or dioxane,
in the presence of an azodicarboxylate such as diethyl
azodicarboxylate, diisopropyl azodicarboxylate or
di(4-chlorobenzyl)azodicarboxylate, and a phosphine such as
triphenylphosphine or tributylphosphine, at temperatures from about
0.degree. C. to about 40.degree. C., for example at about room
temperature (cf. O. Mitsunobu, Synthesis (1981), 1-28).
[0468] Compounds of the formula II for use in the synthesis of
compounds of the formula I in which the groups A, D and E have
other meanings than in the compounds of the formulae IIa and IIb
which are exemplarily discussed above, can likewise be prepared
according to procedures, or analogously to procedures, which are
described in the literature and are generally known to a person
skilled in the art, the synthetic strategy in a specific case being
dependent on the kind of the heterocycle. For example, a procedure
for the synthesis of compounds of the formula II in which A is N, D
is N(R.sup.2) and E is N, i.e. of 5-oxygen-substituted
[1,2,4]triazole-3-carboxylic acid derivatives, which comprises the
alcoholysis of 2-imino-1,3,4-oxadiazole derivatives, is described
in DD 226883. The oxadiazole derivatives may be obtained from
acylhydrazines by reaction with a cyanate as described in M.
Neitzel et al., Arch. Pharm. 313 (1980), 867-878. A procedure for
the synthesis of compounds of the formula II in which A is N, D is
N(R.sup.2) and E is C(R.sup.3), i.e. of 2-oxygen-substituted
imidazole-4-carboxylic acid derivatives, which comprises the
reaction of an alpha-diazo-beta-ketoester with a substituted urea
in the presence of a rhodium catalyst, is described in S.-H. Lee et
al., Org. Lett. 5 (2003), 511-514 and WO 2008/139941. The hydroxy
group in the 2-position of the obtained imidazole derivative can
then by alkylated with triethyloxonium tetrafluoroborate, for
example. A procedure for the synthesis of compounds of the formula
II in which A is C(R.sup.1), D is N(R.sup.2) and E is C(R.sup.3),
i.e. of 5-oxygen-substituted pyrrole-3-carboxylic acid derivatives,
which comprises the reaction of an alpha-dicarbonyl compound with
an N-substituted beta-amino-acrylic acid ester, is described in E.
Caballero et al., Tetrahedron 50 (1994), 7849-7865. A procedure for
the synthesis of compounds of the formula II in which A is N, D is
O and E is C(R.sup.3), i.e. of 2-oxygen-substituted
[1,3]oxazole-4-carboxylic acid derivatives, which comprises the
exchange of the chlorine atom in ethyl
2-chloro-oxazole-3-carboxylate with an oxygen substituent, is
described in G. L. Young et al., Tetrahedron Lett. 45 (2004),
3797-3801; and WO 2007/000582. The 2-chloro-oxazole-3-carboxylate
may be obtained by condensation of ethyl bromopyruvate and urea,
diazotation of the obtained 2-amino-oxazole derivative and
treatment with copper chloride as described in K. J. Hodgetts et
al., Org. Lett. 4 (2002), 2905-2907. A similar procedure for the
synthesis of compounds of the formula II in which A is N, D is S
and E is C(R.sup.3), i.e. of 2-oxygen-substituted
[1,3]thiazole-4-carboxylic acid derivatives, which comprises the
exchange of the bromine atom in ethyl
2-bromo-thiazole-3-carboxylates, which may be obtained from
halo-pyruvates by condensation with thiourea and diazotation of the
obtained 2-amino-thiazole derivative and treatment with a copper
bromide as is also described in T. R. Kelly et al., J. Org. Chem.
61 (1996), 4623-4633, with an oxygen substituent, is described in
WO 94/27983; WO 02/14311 and WO 2009/104155. Likewise further
compounds of the formula II can be prepared.
[0469] The .beta.-amino acids and derivatives of the formula III
are commercially available or can be synthesized by well-known
standard methods, or analogously to such methods, from readily
available starting compounds. For example, for the preparation of
.beta.-amino acids and their alkyl esters of the formula III in
which R.sup.50 and R.sup.60 are hydrogen, can carbonyl compounds of
the formula R.sup.30--C(O)--R.sup.40, in particular aldehydes of
the formula R.sup.32--C(O)--H, be reacted with malonic acid
mono-ethyl ester and ammonia in the presence of a base such as an
alkaline metal hydroxide like potassium hydroxide in a solvent such
as an alcohol like ethanol, as described in V. M. Rodionov et al.,
Izv. Akad. Nauk SSSR, Ser. Khim. (1952), 696-702 (Chem. Abstr. 47
(1953), abstr. no. 61888), or ammonia added to the double bond in
the condensation product of the carbonyl compound with malonic acid
or diethyl malonate and in the case of the condensation product
with diethyl malonate the reaction product treated with an acid
such as hydrochloric acid, as described in V. Scudi, J. Am. Chem.
Soc. 57 (1935), 1279; or M. K. Tse et al., Chem. Eur. J. 12 (2006),
1855-1874, and in the obtained product an ester group hydrolyzed to
the carboxylic acid, or a carboxylic acid group esterified,
respectively, as desired and outlined above. Enantiomerically pure
such compounds of the formula III, for example, can be obtained
from the racemic compounds by crystallization of a salt with an
optically active acid, such as tartaric acid, by stereoselective
enzymatic or microbial degradation, for example as described in the
mentioned article by M. K. Tse et al., or in J. Mano et al.,
Bioscience, Biotechnology and Biochemistry 70 (2006), 1941-1946. In
another strategy for the synthesis of such compounds, in particular
compounds in which R.sup.40, R.sup.50 and R.sup.60 are hydrogen and
R.sup.30 is R.sup.32, the respective 3-substituted acrylic acid,
which can be obtained from the corresponding aldehyde, is converted
into the acid chloride, for example with oxalyl chloride, and the
acid chloride converted with an alcohol into an ester, for example
into the tert-butyl ester using tert-butanol, and the amino group
is then introduced by reaction with the lithium salt of an
optically active amine, for example the lithium salt of
(R)-(+)-N-benzyl-N-(1-phenylethyl)amine, and in the obtained
3-substituted tert-butyl
3-(N-benzyl-N-(1-phenylethyl)amino)propionate the benzyl group and
the phenylethyl group is cleaved off by means of catalytic
hydrogenation (cf. S. G. Davies et al., Tetrahedron: Asymmetry 2
(1991), 183-186); S. G. Davies et al., J. Chem. Soc. Perkin Trans.
1 (1994), 1129-1139).
[0470] The introduction of the structural moieties of the compounds
of the formula in the course of the synthesis can also occur in
another order than outlined above. For example, in the case of
compounds of the formula I in which R.sup.10 is another group than
hydroxy, instead of preparing a compound of the formula II which
contains the group R.sup.10 and reacting it with a compound of the
formula III, also a compound of the formula IIc, which specifically
comprises a hydroxy group in place of the group R.sup.10, can be
reacted with a compound of the formula III, and the obtained
compound of the formula Ia then modified on the hydroxy group by
reaction with a compound of the formula VIII to give a compound of
the formula I in which R.sup.10 is different from hydroxy, i.e. a
compound of the formula Ib. At the end, like in the compounds of
the formula I when prepared as outlined above, any protective
groups in the compounds of the formula Ib may still be deprotected
and/or precursor group converted into the final groups.
##STR00013##
[0471] The groups A, D, E, G, R.sup.30, R.sup.40, R.sup.50 and
R.sup.60 in the compounds of the formulae Ia, Ib and IIc are
defined as in the compounds of the formula I and additionally
functional groups can be present in protected form or in the form
of a precursor group which is later converted into the final group.
The group J in the compounds of the formula IIc is defined as in
the compounds of the formula II. The group R.sup.10a in the
compounds of the formula Ib is defined as in the compounds of the
formulae IIb and VIII. The explanations given above on the reaction
of the compounds of the formulae II and III and the reaction of the
compounds of the formulae IIa and VIII apply correspondingly to the
reaction of the compounds of the formulae IIc and III and the
reaction of the compounds Ia and VIII, respectively.
[0472] For obtaining further compounds of the formula I, various
transformations of functional groups can be carried out under
standard conditions in compounds of the formula I or intermediates
or starting compounds of the synthesis of the compounds of the
formula I. For example, a hydroxy group, including a hydroxy group
representing R.sup.10 in a compound of the formula I, can be
etherified, as outlined above, for example by alkylation with a
halogen compound, for example a bromide or iodide, in the presence
of a base such an alkali metal carbonate like potassium carbonate
or cesium carbonate in an inert solvent such as an amide like DMF
or NMP or a ketone like acetone or butan-2-one, or with the
respective alcohol under the conditions of the Mitsunobu reaction
referred to above. A hydroxy group can be esterified to give a
carboxylic acid ester or a sulfonic acid ester, or converted into a
halide by treatment with a halogenating agent. Halogen atoms can
also be introduced by means of suitable halogenating agents which
replace a hydrogen atom in the starting compound, for example by
means of elemental bromine, sulfuryl chloride or
1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate), which introduce a bromine, chlorine and
fluorine substituent, respectively, for example in the 4-position
of a compound of the formula IIb. A halogen atom can generally be
replaced with a variety of groups in substitution reactions which
may also be transition-metal catalyzed reactions. A nitro group can
be reduced to an amino group, for example by catalytic
hydrogenation. An amino group can be modified under standard
conditions for alkylation, for example by reaction with a halogen
compound or by reductive amination of a carbonyl compound, or for
acylation or sulfonylation, for example by reaction with an
activated carboxylic acid or a carboxylic acid derivate like an
acid chloride or anhydride or a sulfonic acid chloride. A
carboxylic ester group can be hydrolyzed under acidic or basic
conditions to give a carboxylic acid. An acid group can be
activated or converted into a reactive derivative as outlined above
and reacted with an alcohol or an amine or ammonia to give an ester
or amide. A primary amide can be dehydrated to give a nitrile. A
sulfur atom in an alkyl-S-- group or in a heterocyclic ring can be
oxidized with a peroxide like hydrogen peroxide or a peracid to
give a sulfoxide moiety S(O) or a sulfone moiety S(O).sub.2. A
carboxylic acid group, carboxylic acid ester group and a ketone
group can be reduced to an alcohol, for example with a complex
hydride such al lithium aluminium hydride, lithium borohydride or
sodium borohydride, or reacted with an organometallic compound or a
Grignard compound to give an alcohol. Primary and secondary hydroxy
groups can also be oxidized to the oxo groups. All reactions in the
preparation of the compounds of the formula I are known per se and
can be carried out in a manner familiar to a person skilled in the
art according to, or analogously to, procedures which are described
in the standard literature, for example in Houben-Weyl, Methods of
Organic Chemistry, Thieme; or Organic Reactions, John Wiley &
Sons; or R. C. Larock, Comprehensive Organic Transformations: A
Guide to Functional Group Preparations, 2. ed. (1999), John Wiley
& Sons, and the references quoted therein.
[0473] Another subject of the present invention are the novel
starting compounds and intermediates occurring in the synthesis of
the compounds of the formula I, including the compounds of the
formulae Ia, Ib, II, IIa, IIb, IIc, III, V, VI and VIII, wherein
the groups A, D, E, G, J, L, R.sup.2, R.sup.10, R.sup.10a,
R.sup.30, R.sup.40, R.sup.50 and R.sup.60 are defined as above, in
any of their stereoisomeric forms or a mixture of stereoisomeric
forms in any ratio, and their salts, and solvates of any of them,
and their use as synthetic intermediates or starting compounds. All
general explanations, specifications of embodiments and definitions
of numbers and groups given above with respect to the compounds of
the formula I apply correspondingly to the said intermediates and
starting compounds. A subject of the invention are in particular
the novel specific starting compounds and intermediates described
herein. Independently thereof whether they are described as a free
compound and/or as a specific salt, they are a subject of the
invention both in the form of the free compounds and in the form of
their salts, and if a specific salt is described, additionally in
the form of this specific salt.
[0474] The compounds of the formula I inhibit the protease
cathepsin A as can be demonstrated in the pharmacological test
described below and in other tests which are known to a person
skilled in the art. The compounds of the formula I and their
physiologically acceptable salts and solvates therefore are
valuable pharmaceutical active compounds. The compounds of the
formula I and their physiologically acceptable salts and solvates
can be used for the treatment of cardiovascular diseases such as
heart failure including systolic heart failure, diastolic heart
failure, diabetic heart failure and heart failure with preserved
ejection fraction, cardiomyopathy, myocardial infarction, left
ventricular dysfunction including left ventricular dysfunction
after myocardial infarction, cardiac hypertrophy, myocardial
remodeling including myocardial remodeling after infarction or
after cardiac surgery, valvular heart diseases, vascular
hypertrophy, vascular remodeling including vascular stiffness,
hypertension including pulmonary hypertension, portal hypertension
and systolic hypertension, atherosclerosis, peripheral arterial
occlusive disease (PAOD), restenosis, thrombosis and vascular
permeability disorders, ischemia and/or reperfusion damage
including ischemia and/or reperfusion damage of the heart and
ischemia and/or reperfusion damage of the retina, inflammation and
inflammatory diseases such as rheumatoid arthritis and
osteoarthritis, renal diseases such as renal papillary necrosis and
renal failure including renal failure after ischemia/reperfusion,
pulmonary diseases such as cystic fibrosis, chronic bronchitis,
chronic obstructive pulmonary disease (COPD), asthma, acute
respiratory dystress syndrome (ARDS), respiratory tract infections
and lung carcinoma, immunological diseases, diabetic complications
including diabetic nephropathy and diabetic cardiomyopathy,
fibrotic diseases such as pulmonary fibrosis including idiopathic
lung fibrosis, cardiac fibrosis, vascular fibrosis, perivascular
fibrosis, renal fibrosis including renal tubulointerstitial
fibrosis, fibrosing skin conditions including keloid formation,
collagenosis and scleroderma, and liver fibrosis, liver diseases
such as liver cirrhosis, pain such as neuropathic pain, diabetic
pain and inflammatory pain, macular degeneration, neurodegenerative
diseases or psychiatric disorders, or for cardioprotection
including cardioprotection after myocardial infarction and after
cardiac surgery, or for renoprotection, for example. The compounds
of the formula I and their physiologically acceptable salts and
solvates can be used as diuretic (stand-alone treatment or in
combination with established diuretics). The treatment of diseases
is to be understood as meaning both the therapy of existing
pathological changes or malfunctions of the organism or of existing
symptoms with the aim of relief, alleviation or cure, and the
prophylaxis or prevention of pathological changes or malfunctions
of the organism or of symptoms in humans or animals which are
susceptible thereto and are in need of such a prophylaxis or
prevention, with the aim of a prevention or suppression of their
occurrence or of an attenuation in the case of their occurrence.
For example, in patients who on account of their disease history
are susceptible to myocardial infarction, by means of the
prophylactic or preventive medicinal treatment the occurrence or
re-occurrence of a myocardial infarction can be prevented or its
extent and sequelae decreased, or in patients who are susceptible
to attacks of asthma, by means of the prophylactic or preventive
medicinal treatment such attacks can be prevented or their severity
decreased. The treatment of diseases can occur both in acute cases
and in chronic cases. The efficacy of the compounds of the formula
I can be demonstrated in the pharmacological test described below
and in other tests which are known to a person skilled in the art.
The compounds of the formula I with G selected from
R.sup.72--N(R.sup.73)--C(O)-- and their physiologically acceptable
salts and solvates can also be used as prodrugs.
[0475] The compounds of the formula I and their physiologically
acceptable salts and solvates can therefore be used in animals, in
particular in mammals and specifically in humans, as a
pharmaceutical or medicament on their own, in mixtures with one
another or in the form of pharmaceutical compositions. A subject of
the present invention also are the compounds of the formula I and
their physiologically acceptable salts and solvates for use as a
pharmaceutical, as well as pharmaceutical compositions and
medicaments which comprise an efficacious dose of at least one
compound of the formula I and/or a physiologically acceptable salt
thereof and/or solvate thereof as an active ingredient and a
pharmaceutically acceptable carrier, i.e. one or more
pharmaceutically innocuous, or nonhazardous, vehicles and/or
excipients, and optionally one or more other pharmaceutical active
compounds. A subject of the present invention furthermore are the
compounds of the formula I and their physiologically acceptable
salts and solvates for use in the treatment of the diseases
mentioned above or below, including the treatment of any one of the
mentioned diseases, for example the treatment of heart failure,
myocardial infarction, cardiac hypertrophy, diabetic nephropathy,
diabetic cardiomyopathy, cardiac fibrosis, or ischemia and/or
reperfusion damage, or for cardioprotection, the use of the
compounds of the formula I and their physiologically acceptable
salts and solvates for the manufacture of a medicament for the
treatment of the diseases mentioned above or below, including the
treatment of any one of the mentioned diseases, for example the
treatment of heart failure, myocardial infarction, cardiac
hypertrophy, diabetic nephropathy, diabetic cardiomyopathy, cardiac
fibrosis, or ischemia and/or reperfusion damage, or for
cardioprotection, wherein the treatment of diseases comprises their
therapy and prophylaxis as mentioned above, as well as their use
for the manufacture of a medicament for the inhibition of cathepsin
A. A subject of the invention also are methods for the treatment of
the diseases mentioned above or below, including the treatment of
any one of the mentioned diseases, for example the treatment of
heart failure, myocardial infarction, cardiac hypertrophy, diabetic
nephropathy, diabetic cardiomyopathy, cardiac fibrosis, or ischemia
and/or reperfusion damage, or for cardioprotection, which comprise
administering an efficacious amount of at least one compound of the
formula I and/or a physiologically acceptable salt thereof and/or
solvate thereof to a human or an animal which is in need thereof.
The compounds of the formula I and pharmaceutical compositions and
medicaments comprising them can be administered enterally, for
example by oral, sublingual or rectal administration, parenterally,
for example by intravenous, intramuscular, subcutaneous or
intraperitoneal injection or infusion, or by another type of
administration such as topical, percutaneous, transdermal,
intra-articular or intraocular administration.
[0476] The compounds of the formula I and their physiologically
acceptable salts and solvates can also be used in combination with
other pharmaceutical active compounds, wherein in such a
combination use the compounds of the formula I and/or their
physiologically acceptable salts and/or solvates and one or more
other pharmaceutical active compounds can be present in one and the
same pharmaceutical composition or in two or more pharmaceutical
compositions for separate, simultaneous or sequential
administration. Examples of such other pharmaceutical active
compounds are diuretics, aquaretics, angiotensin converting enzyme
(ACE) inhibitors, angiotensin receptor blockers, renin inhibitors,
beta blockers, digoxin, aldosterone antagonists, NO donors,
nitrates, hydralazines, ionotropes, vasopressin receptor
antagonists, soluble guanylate cyclase activators, statins,
peroxisome proliferator-activated receptor-alpha (PPAR-.alpha.)
activators, peroxisome proliferator-activated receptor-gamma
(PPAR-.gamma.) activators, rosiglitazone, pioglitazone, metformin,
sulfonylureas, glucagon-like peptide 1 (GLP-1) agonists, dipeptidyl
peptidase IV (DPPIV) inhibitors, insulins, anti-arrhythmics,
endothelin receptor antagonists, calcium antagonists,
phosphodiesterase inhibitors, phosphodiesterase type 5 (PDE5)
inhibitors, factor II/factor IIa inhibitors, factor IX/factor IXa
inhibitors, factor X/factor Xa inhibitors, factor XIII/factor XIIIa
inhibitors, heparins, glycoprotein IIb/IIIa antagonists, P2Y12
receptor antagonists, clopidogrel, coumarins, cyclooxygenase
inhibitors, acetylsalicylic acid, RAF kinase inhibitors and p38
mitogen-activated protein kinase inhibitors. A subject of the
present invention also is the said combination use of any one or
more of the compounds of the formula I disclosed herein and their
physiologically acceptable salts and solvates, with any one or
more, for example one or two, of the mentioned other pharmaceutical
active compounds.
[0477] The pharmaceutical compositions and medicaments according to
the invention normally contain from about 0.5 to about 90 percent
by weight of compounds of the formula I and/or physiologically
acceptable salts and/or solvates thereof, and an amount of active
ingredient of the formula I and/or its physiologically acceptable
salt and/or solvate which in general is from about 0.2 mg to about
1.5 g, particularly from about 0.2 mg to about 1 g, more
particularly from about 0.5 mg to about 0.5 g, for example from
about 1 mg to about 0.3 g, per unit dose. Depending on the kind of
the pharmaceutical composition and other particulars of the
specific case, the amount may deviate from the indicated ones. The
production of the pharmaceutical compositions and medicaments can
be carried out in a manner known per se. For this, the compounds of
the formula I and/or their physiologically acceptable salts and/or
solvates are mixed together with one or more solid or liquid
vehicles and/or excipients, if desired also in combination with one
or more other pharmaceutical active compounds such as those
mentioned above, and brought into a suitable form for dosage and
administration, which can then be used in human medicine or
veterinary medicine.
[0478] As vehicles, which may also be looked upon as diluents or
bulking agents, and excipients suitable organic and inorganic
substances can be used which do not react in an undesired manner
with the compounds of the formula I. As examples of types of
excipients, or additives, which can be contained in the
pharmaceutical compositions and medicaments, lubricants,
preservatives, thickeners, stabilizers, disintegrants, wetting
agents, agents for achieving a depot effect, emulsifiers, salts,
for example for influencing the osmotic pressure, buffer
substances, colorants, flavorings and aromatic substances may be
mentioned. Examples of vehicles and excipients are water, vegetable
oils, waxes, alcohols such as ethanol, isopropanol,
1,2-propanediol, benzyl alcohols, glycerol, polyols, polyethylene
glycols or polypropylene glycols, glycerol triacetate,
polyvinylpyrrolidone, gelatin, cellulose, carbohydrates such as
lactose or starch like corn starch, sodium chloride, stearic acid
and its salts such as magnesium stearate, talc, lanolin, petroleum
jelly, or mixtures thereof, for example saline or mixtures of water
with one or more organic solvents such as mixtures of water with
alcohols. For oral and rectal use, pharmaceutical forms such as,
for example, tablets, film-coated tablets, sugar-coated tablets,
granules, hard and soft gelatin capsules, suppositories, solutions,
including oily, alcoholic or aqueous solutions, syrups, juices or
drops, furthermore suspensions or emulsions, can be used. For
parenteral use, for example by injection or infusion,
pharmaceutical forms such as solutions, for example aqueous
solutions, can be used. For topical use, pharmaceutical forms such
as ointments, creams, pastes, lotions, gels, sprays, foams,
aerosols, solutions or powders can be used. Further suitable
pharmaceutical forms are, for example, implants and patches and
forms adapted to inhalation. The compounds of the formula I and
their physiologically acceptable salts can also be lyophilized and
the obtained lyophilizates used, for example, for the production of
injectable compositions. In particular for topical application,
also liposomal compositions are suitable. The pharmaceutical
compositions and medicaments can also contain one or more other
active ingredients and/or, for example, one or more vitamins.
[0479] As usual, the dosage of the compounds of the formula I
depends on the circumstances of the specific case and is adjusted
by the physician according to the customary rules and procedures.
It depends, for example, on the compound of the formula I
administered and its potency and duration of action, on the nature
and severity of the individual syndrome, on the sex, age, weight
and the individual responsiveness of the human or animal to be
treated, on whether the treatment is acute or chronic or
prophylactic, or on whether further pharmaceutical active compounds
are administered in addition to a compound of the formula I.
Normally, in the case of administration to an adult weighing about
75 kg, a dose from about 0.1 mg to about 100 mg per kg per day, in
particular from about 1 mg to about 20 mg per kg per day, for
example from about 1 mg to about 10 mg per kg per day (in each case
in mg per kg of body weight), is administered. The daily dose can
be administered in the form of a single dose or divided into a
number of individual doses, for example two, three or four
individual doses. The administration can also be carried out
continuously, for example by continuous injection or infusion.
Depending on the individual behavior in a specific case, it may be
necessary to deviate upward or downward from the indicated dosages.
Besides as a pharmaceutical active compound in human medicine and
veterinary medicine, the compounds of the formula I can also be
employed as an aid in biochemical investigations or as a scientific
tool or for diagnostic purposes, for example in in-vitro diagnoses
of biological samples, if an inhibition of cathepsin A is intended.
The compounds of the formula I and their salts can also be used as
intermediates, for example for the preparation of further
pharmaceutical active substances.
[0480] The following examples illustrate the invention.
ABBREVIATIONS
[0481] ACN acetonitrile [0482] DCM dichloromethane [0483] DMF
N,N-dimethylformamide [0484] DMSO dimethyl sulfoxide [0485] EA
ethyl acetate [0486] EDIA N-ethyl-diisopropylamine [0487] FA formic
acid [0488] MOH methanol [0489] NEM N-ethyl-morpholine [0490] TFA
trifluoroacetic acid [0491] THF tetrahydrofuran [0492] TOTU
O-(cyano(ethoxycarbonyl)methyleneamino)-N,N,N',N'-tetramethyluronium
tetrafluoroborate
[0493] When example compounds containing a basic group were
purified by preparative high pressure liquid chromatography (HPLC)
on reversed phase (RP) column material and, as customary, the
eluent was a gradient mixture of water and acetonitrile containing
trifluoroacetic acid, they were in part obtained in the form of
their acid addition salts with trifluoroacetic acid, depending on
the details of the work-up such as evaporation or lyophilization
conditions. In the names of the example compounds and the
structural formulae such contained trifluoroacetic acid is not
specified. Likewise are other acid components of example compounds
obtained in the form of an acid addition salt in general not
specified in the name and the formula.
[0494] The prepared compounds were in general characterized by
spectroscopic data and chromatographic data, in particular mass
spectra (MS) and HPLC retention times (Rt; in min) which were
obtained by combined analytical HPLC/MS characterization (LC/MS),
and/or nuclear magnetic resonance (NMR) spectra. Unless specified
otherwise, .sup.1H-NMR spectra were recorded at 500 MHz in
D.sub.6-DMSO as solvent at 298 K. In the NMR characterization, the
chemical shift .delta. (in ppm), the number of hydrogen atoms (H),
and the multiplicity (s: singlet, d: doublet, dd: doublet of
doublets, t: triplet, q: quartet, m: multiplet) of the peaks as
determined from the graphically depicted spectra are given. In the
MS characterization, in general the mass number (m/z) of the peak
of the molecular ion [M], for example [M.sup.+], or of a related
ion such as the ion [M+1], for example [(M+1).sup.+], i.e. the
protonated molecular ion [(M+H).sup.+], or the ion [M-1], for
example [(M-1).sup.-], i.e. the deprotonated molecular ion
[(M-H).sup.-], which was formed depending on the ionization method
used, is given. Generally, the ionization method was electrospray
ionization (ES). The particulars of the LC/MS methods used are as
follows.
Method LC1
[0495] Column: YMC-Pack Jsphere H80, 33.times.2.1 mm, 4 .mu.m;
flow: 1.3 ml/min; room temperature; eluent A: water+0.05% TFA;
eluent B: ACN+0.05% TFA; gradient: from 95% A+5% B to 5% A+95% B
within 2.5 min; MS ionization method: ES.sup.+
Method LC2
[0496] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.3 ml/min; room temperature; eluent A: water+0.1% FA; eluent
B: ACN+0.08% FA; gradient: from 97% A+3% B to 40% A+60% B within
3.5 min, then to 2% A+98% B within 0.5 min, then 2% A+98% B for 1.0
min, then to 97% A+3% B within 0.2 min, then 97% A+3% B for 1.3
min; MS ionization method: ES.sup.-
Method LC3
[0497] Column: YMC-Pack Jsphere H80, 33.times.2.1 mm, 4 .mu.m;
flow: 1.0 ml/min; room temperature; eluent A: water+0.05% TFA;
eluent B: ACN+0.05% TFA; gradient: 98% A+2% B for 1.0 min, then to
5% A+95% B within 4.0 min, then 5% A+95% B for 1.25 min; MS
ionization method: ES.sup.+
Method LC4
[0498] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.3 ml/min; 40.degree. C.; eluent A: water+0.1% FA; eluent B:
ACN+0.1% FA; gradient: from 97% A+3% B to 40% A+60% B within 3.5
min, then to 2% A+98% B within 0.5 min, then 2% A+98% B for 1.0
min, then to 97% A+3% B within 0.2 min, then 97% A+3% B for 1.3
min; MS ionization method: ES.sup.-
Method LC5
[0499] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.7 ml/min; 40.degree. C.; eluent A: water+0.05% TFA; eluent
B: ACN+0.05% TFA; gradient: from 95% A+5% B to 5% A+95% B within
3.3 min, then 5% A+95% B for 0.55 min, then to 95% A+5% B within
0.15 min; MS ionization method: ES.sup.+
Method LC6
[0500] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.7 ml/min; 50.degree. C.; eluent A: water+0.05% TFA; eluent
B: ACN+0.05% TFA; gradient: 95% A+5% B for 0.2 min, then to 5%
A+95% B within 2.2 min, then 5% A+95% B for 1.1 min, then to 95%
A+5% B within 0.1 min, then 95% A+5% B for 0.9 min; MS ionization
method: ES.sup.+
Method LC7
[0501] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.7 ml/min; 40.degree. C.; eluent A: water+0.05% TFA; eluent
B: ACN+0.05% TFA; gradient: 95% A+5% B for 0.2 min, then to 5%
A+95% B within 2.2 min, then 5% A+95% B for 0.8 min, then to 95%
A+5% B within 0.1 min, then 95% A+5% B for 0.7 min; MS ionization
method: ES.sup.+
Method LC8
[0502] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.7 ml/min; 40.degree. C.; eluent A: water+0.05% TFA; eluent
B: ACN+0.05% TFA; gradient: 95% A+5% B for 0.3 min, then to 5%
A+95% B within 3.2 min, then 5% A+95% B for 0.5 min; MS ionization
method: ES.sup.+
Method LC9
[0503] Column: Merck Chromolith FastGrad RP-18e, 50.times.2 mm;
flow: 2.0 ml/min; room temperature; eluent A: water+0.05% TFA;
eluent B: ACN+0.05% TFA; gradient: 98% A+2% B for 0.2 min, then to
2% A+98% B within 2.2 min, then 2% A+98% B for 0.8 min, then to 98%
A+2% B within 0.1 min, then 98% A+2% B for 0.7 min; MS ionization
method: ES.sup.+
Method LC10
[0504] Column: Waters XBridge C18, 50.times.4.6 mm, 2.5 .mu.m;
flow: 1.3 ml/min; 45.degree. C.; eluent A: water+0.1% FA; eluent B:
ACN+0.1% FA; gradient: from 97% A+3% B to 40% A+60% B within 3.5
min, then to 2% A+98% B within 0.5 min, then 2% A+98% B for 1.0
min, then to 97% A+3% B within 0.2 min, then 97% A+3% B for 1.3
min; MS ionization method: ES.sup.+
Method LC11
[0505] Column: Waters UPLC BEH C18, 50.times.2.1 mm, 1.7 .mu.m;
flow: 0.9 ml/min; 55.degree. C.; eluent A: water+0.1% FA; eluent B:
ACN+0.08% FA; gradient: from 95% A+5% B to 5% A+95% B within 1.1
min, then 5% A+95% B for 0.6 min, then to 95% A+5% B within 0.1
min, then 95% A+5% B for 0.2 min; MS ionization method:
ES.sup.+
Method LC12
[0506] Column: YMC-Pack Jsphere H80, 33.times.2.1 mm, 4 .mu.m;
flow: 1.0 ml/min; room temperature; eluent A: water+0.05% TFA;
eluent B: MOH+0.05% TFA; gradient: 98% A+2% B for 1.0 min, then to
5% A+95% B within 4.0 min, then 5% A+95% B for 1.25 min; MS
ionization method: ES.sup.+
Method LC13.
[0507] Column: Waters XBridge C18, 50.times.4.6, 2.5 .mu.m; flow:
1.3 ml/min; room temperature; eluent A: water+0.1% FA; eluent B:
ACN+0.08% FA; gradient: from 97% A+3% B to 2% A+98% B within 18.0
min, then 2% A+98% B for 1.0 min, then to 97% A+3% B within 0.5
min, then 97% A+3% B for 0.5 min; MS ionization method:
ES.sup.+
Method LC14
[0508] Column: Waters XBridge C18 4.6*50 mm; 2.5 um, flow: 1.3
ml/min; eluent A H.sub.2O+0.1% FA; eluent B: ACN+0.08% FA;
gradient: from 97% A+3% B to 2% A+98% B within 18 min, then 2%
A+98% B for 1 min, then to 97% A+3% B within 0.5 min then to 97:3
for 0.5 min.
SYNTHESIS EXAMPLE 1
1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid
##STR00014##
[0510] Sulfuric acid (400 ml) was added slowly to water (400 ml).
After cooling to 5.degree. C., 2-fluoro-phenylhydrazine
hydrochloride (123 g, 757 mmol) was added resulting in a brown
suspension. Then a solution of oxalacetic acid (100 g, 757 mmol) in
water (400 ml) was added slowly during a period of 25 min. After 2
h the conversion was complete and the solid was filtered. After
washing with water the solid was dried. The product was obtained as
light brown solid (151 g, 90%).
[0511] Analogously as described in synthesis example 1, the
following compounds were prepared: [0512]
5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylic acid [0513]
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid [0514]
1-(2,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid
[0515] 1-(3,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0516] 1-(2-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0517] 1-(3-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0518] 1-(4-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0519]
1-(3-chloro-4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0520] 5-hydroxy-1-(3-methoxy-phenyl)-1H-pyrazole-3-carboxylic
acid [0521]
1-(2-chloro-pyridin-4-yl)-5-hydroxy-1H-pyrazole-3-carboxylic acid
[0522] 1-(5-chloro-pyridin-2-yl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0523]
5-hydroxy-1-(4-trifluoromethyl-pyrimidin-2-yl)-1H-pyrazole-3-carbo-
xylic acid [0524]
5-hydroxy-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylic acid [0525]
5-hydroxy-1-(pyridin-3-yl)-1H-pyrazole-3-carboxylic acid [0526]
5-hydroxy-1-(2-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic
acid [0527]
5-hydroxy-1-(3,5-difluoro-phenyl)-1H-pyrazole-3-carboxylic acid
[0528] 5-hydroxy-1-(2,5-difluoro-phenyl)-1H-pyrazole-3-carboxylic
acid [0529]
5-hydroxy-1-(2,6-difluoro-phenyl)-1H-pyrazole-3-carboxylic acid
[0530]
1-(3-chloro-2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic
acid [0531] 1-cyclopentyl-5-hydroxy-1H-pyrazole-3-carboxylic acid
[0532] 1-cyclohexyl-5-hydroxy-1H-pyrazole-3-carboxylic acid [0533]
5-hydroxy-1-(3-sulfamoyl-phenyl)-1H-pyrazole-3-carboxylic acid
[0534]
5-hydroxy-1-(2-methanesulfonyl-phenyl)-1H-pyrazole-3-carboxylic
acid [0535] 1-tert-butyl-5-hydroxy-1H-pyrazole-3-carboxylic
acid
SYNTHESIS EXAMPLE 2
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-o-t-
olyl-propionic acid
##STR00015##
[0537] 0.45 mmol of
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid were
dissolved in 5 ml of DMF, 0.54 mmol of TOTU and 1.125 mmol of NEM
were added, and the mixture was stirred for 5 min at room
temperature. Then 0.495 mmol of (S)-3-amino-3-o-tolyl-propionic
acid were added and the mixture stirred overnight at room
temperature. The solvent was evaporated in vacuo and the residue
subjected to preparative HPLC to give the title compound in a yield
of 28%.
SYNTHESIS EXAMPLE 3
5-Methoxy-1-phenyl-1H-pyrazole-3-carboxylic acid
##STR00016##
[0539] 600 mg (2.94 mmol) of
5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylic acid were dissolved in
30 ml of DMF, 1.92 (5.9 mmol) of cesium carbonate and 1.04 g (7.35
mmol) of iodomethane were added, and the resulting mixture was
heated for 4 h to 80.degree. C. The mixture was filtrated and the
solvent removed in vacuo. The residue was dissolved in 20 ml of MOH
and 5.9 ml of an aqueous 1 M solution of sodium hydroxide. After
stirring overnight the reaction was complete. The solvent was
removed and the residue subjected to preparative HPLC to give the
title compound in a yield of 38%. Analogously as described in
synthesis example 3, the following compounds were prepared: [0540]
1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid [0541]
1-(2-chloro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid [0542]
1-(3-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid [0543]
1-(2,5-difluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[0544] 1-tert-butyl-5-methoxy-1H-pyrazole-3-carboxylic acid
SYNTHESIS EXAMPLE 4
Methyl 1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate
##STR00017##
[0546] 1 g (4.5 mmol) of
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid was
dissolved in 20 ml of MOH. 535 mg (4.5 mmol) of thionyl chloride
was added with caution and the mixture is stirred for 4 h at room
temperature. Then the solvent was removed in vacuo to give 900 mg
(85%) of the crude title compound which was used in the following
step without further purification.
SYNTHESIS EXAMPLE 5
Methyl 1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate
##STR00018##
[0548] Dimethyl acetylenedicarboxylate (87.4 g, 757 mmol) was added
to a solution of 2-fluoro-phenylhydrazine hydrochloride (100 g, 615
mmol) in methanol (1 l) at 0.degree. C. Then triethylamine (125 g,
1.23 mol) was added slowly during 60 min. The solution was stirred
for 16 h at room temperature, the solvent then removed under
reduced pressure and the residue dissolved in EA (500 ml). After
washing with aqueous hydrochloric acid (500 ml), the solvent was
removed under reduced pressure. The title compound was obtained as
an almost white solid in quantitative yield.
SYNTHESIS EXAMPLE 6
5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid
##STR00019##
[0549] Step 1:
5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid methyl ester
[0550] 150 mg (0.635 mmol) of methyl
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate were
dissolved in 8 ml of THF. 207 mg (0.635 mmol) of cesium carbonate
and 400 mg (2.96 mmol) of bromomethyl-cyclopropane were added and
the mixture was heated to 50.degree. C. for 6 h. Then the mixture
was filtrated and the solvent removed in vacuo. The crude title
compound was used in the next step without further
purification.
Step 2:
5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid
[0551] The crude compound obtained in step 1 was dissolved in 10 ml
of methanol. 1.4 ml of an aqueous 1 M solution of sodium hydroxide
were added and the mixture was stirred overnight at room
temperature. The solvent was removed in vacuo and the residue
purified by preparative HPLC to give 102 mg (58%) of the title
compound Analogously as described in synthesis example 6, the
following compounds were prepared: [0552]
5-cyclopropylmethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid [0553]
5-cyclopropylmethoxy-1-(2,6-difluoro-phenyl)-1H-pyrazole-3-carboxylic
acid [0554]
5-dimethylcarbamoyl-methoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid (using 2 equivalents of 2-chloro-N,N-dimethyl-acetamide
instead of bromomethyl-cyclopropane in step 1) [0555]
1-(2-fluoro-phenyl)-5-(2-oxo-2-pyrrolidin-1-yl-ethoxy)-1H-pyrazole-3-carb-
oxylic acid (using 2 equivalents of
2-chloro-1-pyrrolidin-1-yl-ethanone instead of
bromomethyl-cyclopropane in step 1)
SYNTHESIS EXAMPLE 7
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
##STR00020##
[0556] Step 1: Methyl
1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylate
[0557] Potassium carbonate (27.8 g, 201 mmol) and water (3.62 g,
201 mmol) were added to a suspension of methyl
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate (31.6 g,
134 mmol) in methyl isobutyl ketone (323 ml) at room temperature.
Then dimethyl sulfate (16.9 g, 134 mmol) was added slowly and the
mixture was stirred for 2.5 h. Water was added and the phases were
separated. The organic phase was evaporated to give 27.4 g of the
title compound as a white solid.
Step 2: 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
[0558] 109 ml of an aqueous 2 M solution of sodium hydroxide (218
mmol) were added to a solution of the crude methyl ester obtained
in step 1 in methyl isobutyl ketone. After 16 h at room temperature
the conversion was complete and the phases were separated. The
aqueous phase was acidified to pH 3 with hydrochloric acid and
extracted with EA. The organic phases were evaporated to give 18.9
g (59% over two steps) of the title compound.
[0559] Analogously as described in synthesis example 7, the
following compounds were prepared, using diethyl sulfate instead of
dimethyl sulfate in step 1: [0560]
5-ethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid [0561]
5-ethoxy-1-(2-chloro-phenyl)-1H-pyrazole-3-carboxylic acid [0562]
5-ethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid
SYNTHESIS EXAMPLE 8
Ethyl (S)-3-amino-3-(2-methyl-phenyl)-propionate
##STR00021##
[0564] (S)-3-Amino-3-(2-methyl-phenyl)propionic acid (10.0 g, 55.8
mmol) was suspended in 2-methyltetrahydrofuran (100 ml) and ethanol
(25.7 g, 558 mmol) was added. The mixture was heated to 80.degree.
C. and thionyl chloride (6.64 g, 55.8 mmol) was added slowly. After
2 h at 80.degree. C. the solvents were almost completely removed by
distillation. After cooling the mixture was stirred at room
temperature for 16 h. Then more solvent was removed under reduced
pressure to give the title compound in the form of ethyl
(S)-3-amino-3-(2-methyl-phenyl)-propionate hydrochloride together
with some 2-methyltetrahydrofuran in quantitative yield.
SYNTHESIS EXAMPLE 9
Ethyl
(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-
-3-(2-methyl-phenyl)-propionate
##STR00022##
[0565] Step 1: 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl
chloride
[0566] A suspension of
1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid (39.1
g, 167 mmol) in 2-methyltetrahydrofuran (300 ml) was cooled to
0.degree. C. and DMF (293 .mu.l, 3.81 mmol) was added. Oxalyl
chloride (23.1 g, 182 mmol) was added dropwise. After 16 h at room
temperature ca. 100 ml of the solvent were removed by distillation.
The resulting suspension of the title compound was used directly in
the next step.
Step 2: Ethyl
(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-
-methyl-phenyl)-propionate
[0567] A solution of ethyl
(S)-3-amino-3-(2-methyl-phenyl)-propionate hydrochloride (42.4 g,
174 mmol) in 2-methyltetrahydrofuran (200 ml) was added to the
suspension of 1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl
chloride in ca. 200 ml of 2-methyltetrahydrofuran obtained in step
1. Triethylamine (33.5 g, 331 mmol) was added dropwise under ice
cooling. After the complete addition of the triethylamine the
conversion was complete and water was added. The phases were
separated and the organic phase was washed with water and
evaporated. The residue was dissolved in 2-methyltetrahydrofuran
(500 ml) and washed with 1 M hydrochloric acid. The organic phase
was dried and the solvent was removed under reduced pressure to
give 70.4 g (99% over two step) of the title compound as a light
brown oil.
SYNTHESIS EXAMPLE 10
(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2--
methyl-phenyl)-propionic acid
##STR00023##
[0569] 82.8 ml of an aqueous 4 M solution of sodium hydroxide (331
mmol) were added to a solution of ethyl
(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-
-methyl-phenyl)-propionate (70.4 g, 165 mmol) in
2-methyltetrahydrofuran (500 ml) at room temperature. The mixture
was stirred at room temperature for 2 h, then at 40.degree. C. for
2 h and then at room temperature for 16 h. The phases were
separated and the aqueous phase acidified to pH 3 with hydrochloric
acid. The product partially precipitated upon acidification. The
aqueous filtrate was extracted with EA. The extracts were
evaporated and the residue was washed with isopropyl acetate. The
two batches were combined to give 53.6 g (82%) of the title
compound as a white crystalline powder.
SYNTHESIS EXAMPLE 11
5-(2-Cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid
##STR00024##
[0571] 1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid
methyl ester (200 mg, 0.847 mmol) were dissolved in 5 ml of DMF and
cesium carbonate (552 mg, 1.7 mmol) and 2-bromomethyl-benzonitrile
(166 mg, 0.85 mmol) were added. The mixture was stirred for 5 h at
60.degree. C., filtrated and the solvent was removed in vacuo. The
obtained residue of crude
5-(2-cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid methyl ester (235 mg, 79%) was dissolved in a mixture of THF,
MOH and water (3 ml each), lithium hydroxide (64.1 mg, 2.7 mmol)
was added, and the mixture was stirred overnight at room
temperature. After evaporation of the solvent the residue was
subjected to column chromatography (silica gel, DCM/MOH 9:1) to
give 195 mg (86%) of the title compound.
SYNTHESIS EXAMPLE 12
(S)-3-{[5-(2-Cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]--
amino}-3-O-- tolyl-propionic acid ethyl ester
##STR00025##
[0573] 190 mg (0.56 mmol) of
(2-cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid were dissolved in 6 ml of DMF, and 213.5 mg (0.56 mmol) of
O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate and 145.5 mg (1.12 mmol) of NEM were added.
Then 116.7 mg (0.56 mmol) of ethyl
(S)-3-amino-3-(2-methyl-phenyl)-propionate were added and the
mixture was stirred for 3 h at room temperature. The solvent was
removed in vacuo and the residue subjected to column chromatography
(silica gel, DCM/MOH 100:1) to give 210 mg (71%) of the title
compound.
SYNTHESIS EXAMPLE 13
(S)-3-{[5-(2-Cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbon
yl]-amino}-3-o-tolyl-propionic acid
##STR00026##
[0575] 210 mg (0.4 mmol) of
(S)-3-{[5-(2-cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-
-amino}-3-o-tolyl-propionic acid ethyl ester were dissolved in a
mixture of THF, MOH and water (2 ml each), lithium hydroxide (28.7
mg, 1.2 mmol) was added, and the mixture was stirred for 3 h at
room temperature. After evaporation of the solvent the residue was
subjected to aqueous work-up using EA and a 10% aqueous solution of
citric acid. After evaporation of the organic phase the residue was
subjected to column chromatography (silica gel, DCM/MOH 10:1) to
give 45 mg (23%) of the title compound.
SYNTHESIS EXAMPLE 14
(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl-oxetan-3-ylmethoxy)-1H-pyrazole-3--
carbonyl]-amino}-3-(2-methyl-phenyl)-propionic acid ethyl ester
##STR00027##
[0577] 101 mg (0.245 mmol) of
(S)-3-{[1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-
-methyl-phenyl)-propionic acid ethyl ester (prepared from
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid and
ethyl (S)-3-amino-3-(2-methyl-phenyl)-propionate analogously as
described in synthesis example 2) were dissolved in 3 ml of DMF,
and 160 mg (0.5 mmol) of cesium carbonate and 41.3 mg (0.245 mmol)
of 3-bromomethyl-3-methyl-oxetane were added. The mixture was
stirred for 4 h at 65.degree. C. After evaporation of the solvent
the residue was subjected to an aqueous work-up with EA and 10%
aqueous solution of citric acid. After removal of the solvent from
the organic phase 100 mg (82%) of the product are obtained.
SYNTHESIS EXAMPLE 15
(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl-oxetan-3-ylmethoxy)-1H-pyrazole-3--
carbonyl]-amino}-3-(2-methyl-phenyl)-propionic acid
##STR00028##
[0579] 100 mg (0.2 mmol) of
(S)-3-{[1-(2-fluoro-phenyl)-5-(3-methyl-oxetan-3-ylmethoxy)-1H-pyrazole-3-
-carbonyl]-amino}-3-(2-methyl-phenyl)-propionic acid ethyl ester
were dissolved in a mixture of THF, MOH and water (2 ml each), and
14.5 mg (0.61 mmol) of lithium hydroxide were added. The mixture
was stirred overnight at room temperature and the solvent removed.
The residue was subjected to column chromatography (silica gel,
DCM/MOH 9:1) to give 75 mg (75%) of the title compound.
SYNTHESIS EXAMPLE 16
Pyrrolidine-1-carboxylic acid
5-((S)-2-carboxy-1-o-tolyl-ethylcarbamoyl)-2-(2-fluoro-phenyl)-2H-pyrazol-
-3-yl ester
##STR00029##
[0580] Step 1:
1-(2-Fluoro-phenyl)-5-(pyrrolidine-1-carbonyloxy)-1H-pyrazole-3-carboxyli-
c acid
[0581] 150 mg (0.675 mmol) of
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid were
dissolved in 5 ml of THF. 440 mg (1.35 mmol) of cesium carbonate
and 90.2 mg (0.675 mmol) of pyrrolidine-1-carbonyl chloride were
added and the mixture was heated to 50.degree. C. for 4 h. Then the
mixture was filtrated and the filtrate containing the title
compound directly used in the next step.
Step 2: Pyrrolidine-1-carboxylic acid
5-((S)-2-carboxy-1-o-tolyl-ethylcarbamoyl)-2-(2-fluoro-phenyl)-2H-pyrazol-
-3-yl ester
[0582] 0.675 mmol of TOTU and 1.35 mmol of EDIA were added to the
filtrate containing
1-(2-fluoro-phenyl)-5-(pyrrolidine-1-carbonyloxy)-1H-pyrazole-3-carboxyli-
c acid obtained in step 1. The mixture was stirred for 5 min at
room temperature, and then 0.675 mmol of
(S)-3-amino-3-(2-methyl-phenyl)-propionic acid were added and the
mixture was stirred overnight at RT. Then the solvent was
evaporated and the residue subjected to preparative HPLC to give
the title compound in a yield of 67%.
[0583] Analogously as described in synthesis example 16, step 1,
the following compounds were prepared: [0584]
5-dimethylcarbamoyloxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid [0585]
1-(2-fluoro-phenyl)-5-(piperidine-1-carbonyloxy)-1H-pyrazole-3-car-
boxylic acid [0586]
1-(2-fluoro-phenyl)-5-(methyl-phenyl-carbamoyloxy)-1H-pyrazole-3-carboxyl-
ic acid
SYNTHESIS EXAMPLE 17
4-Bromo-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
##STR00030##
[0588] 50 mg (0.21 mmol) of
1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid were
dissolved in 1.5 ml of acetic acid, sodium acetate (35 mg, 0.42
mmol) and bromine (50 mg, 0.21 mmol) were added and the mixture was
stirred for 60 min. The solvent was removed in vacuo and the
residue subjected to an aqueous work-up. The obtained crude title
compound (60 mg) was used in the next step without further
purification.
SYNTHESIS EXAMPLE 18
4-Chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
##STR00031##
[0589] Step 1:
4-Chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid methyl ester
[0590] 300 mg (1.2 mmol) of
1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid methyl
ester was dissolved in 3 ml of acetic acid. 162 mg (1.2 mmol) of
sulfuryl chloride were added and the mixture stirred for 4 h at
room temperature. The solvent was removed in vacuo and the residue
subjected to acidic aqueous work-up. The obtained crude title
compound (330 mg) was used in the hydrolysis step without further
purification.
Step 2:
4-Chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
[0591] The crude
4-chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid methyl ester obtained (330 mg, 1.16 mmol) obtained in step 1
was dissolved in 6 ml of dioxane and 5.8 ml of an aqueous 1 M
solution of lithium hydroxide were added. The mixture was stirred
for 30 min at 56.degree. C. Acidic aqueous work-up gave 320 mg
(100%) of the title compound.
SYNTHESIS EXAMPLE 19
4-Fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
##STR00032##
[0592] Step 1:
4-Fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid methyl ester
[0593] 200 mg (0.8 mmol) of
1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid methyl
ester were dissolved in 2 ml of acetonitrile and 745 mg (1.99 mmol)
of 1-chloro-methyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate) (Selectfluor.RTM.) were added. The mixture
was stirred overnight. Then, irrespective of the incomplete
reaction, diethyl ether, water and 2 N hydrochloric acid were
added, the organic phase was separated, the solvent evaporated and
the residue subjected to preparative HPLC. 70 mg (33%) of the title
compound were obtained.
Step 2:
4-Fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid
[0594] 70 mg (0.26 mmol) of
4-fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic
acid methyl ester were dissolved in 1.3 ml of dioxane and 1.305 ml
of a 1 M aqueous solution of lithium hydroxide were added. The
mixture was stirred at 56.degree. C. for 30 min, then water and 2 N
hydrochloric acid were added and the mixture extracted with diethyl
ether. The organic phase was evaporated to give 67 mg (33%) of the
title compound.
SYNTHESIS EXAMPLE 20
1-(2-Fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylic acid
##STR00033##
[0595] Step 1: Methyl
1-(2-fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylate
[0596] 150 mg (0.635 mmol) of
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid methyl
ester, 166.6 mg (0.635 mmol) of triphenylphosphine and 38.16 mg
(0.635 mmol) of 2-propanol were dissolved in 1.5 ml of DCM, and
then a solution of 0.635 mmol of di(4-chlorobenzyl)
azodicarboxylate in 1.5 ml of DCM was added. After stirring at room
temperature for 4 h, the mixture was filtered and the solvent
removed in vacuo. The obtained crude title compound was used in the
hydrolysis step without further purification.
Step 2: 1-(2-Fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylic
acid
[0597] The crude methyl
1-(2-fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylate obtained
in step 1 was dissolved in 6 ml of MOH, 2 ml of an aqueous 1 M
solution of sodium hydroxide were added, and the mixture was
stirred for 5 h at 40.degree. C. The solvent was removed and the
residue subjected to acidic aqueous work-up to give 70% of the
title compound.
SYNTHESIS EXAMPLE 21
(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2--
methyl-phenyl)-propionic acid amide
##STR00034##
[0599] DMF (1.8 mg, 25 .mu.mol) and oxalyl chloride (160 mg, 1.26
mmol) were added to a solution of
(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-
-methyl-phenyl)-propionic acid (500 mg, 1.26 mmol) in DCM (5 ml) at
room temperature. After 16 h at room temperature a 33% aqueous
solution of ammonia (649 mg, 12.6 mmol) was added and the mixture
was stirred for further 16 h. The solvent was removed under reduced
pressure and the residue was purified by preparative HPLC to give
170 mg (34%) of the title compound as a colorless oil.
SYNTHESIS EXAMPLE 22
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-ca-
rbonyl]-amino}-3-o-tolyl-propionic acid
##STR00035##
[0600] Step 1:
5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxyli-
c acid methyl ester
[0601] 200 mg (0.85 mmol) of
1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid methyl
ester were dissolved in 5 ml of DMF. 552 mg (1.7 mmol) of cesium
carbonate and 152 mg (0.85 mmol) of
1-bromo-3,3-dimethyl-butan-2-one were added and the mixture was
heated to 50.degree. C. for 6 h. Then the mixture was filtered and
the solvent removed in vacuo. The obtained crude title compound was
subjected to hydrolysis without further purification.
Step 2:
5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-ca-
rboxylic acid
[0602] 100 mg (0.3 mmol) of
5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxyli-
c acid methyl ester were dissolved in 5 ml of MOH. 0.7 mmol of
lithium hydroxide and 2 ml of water were added and the mixture
stirred overnight at room temperature. The solvent was removed in
vacuo and the residue subjected to aqueous work-up with a 10%
solution of citric acid and DCM. The organic phase was dried and
the solvent removed in vacuo to give the title compound.
Step 3:
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyraz-
ole-3-carbonyl]-amino}-3-o-tolyl-propionic acid
[0603] 324 mg (0.675 mmol) of
5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxyli-
c acid were dissolved in 5 ml of DMF and 0.675 mmol of TOTU and
1.35 mmol of EDIA were added. The mixture was stirred for 5 min at
room temperature, then 0.675 mmol of
(S)-3-amino-3-(2-methyl-phenyl)-propionic acid were added and the
mixture was stirred overnight at room temperature. After
evaporation of the solvent, the residue was subjected to
preparative HPLC to give the title compound in a yield of 67%.
[0604] Analogously as described in synthesis example 22, steps 1
and 2, the following compounds were prepared, using chloro-acetone,
1-bromo-butan-2-one and 2-bromo-1-cyclopropyl-ethanone,
respectively, instead of 1-bromo-3,3-dimethyl-butan-2-one in step
1: [0605]
1-(2-fluoro-phenyl)-5-(2-oxo-propoxy)-1H-pyrazole-3-carboxylic acid
[0606]
1-(2-fluoro-phenyl)-5-(2-oxo-butoxy)-1H-pyrazole-3-carboxylic acid
[0607]
5-(2-cyclopropyl-2-oxo-ethoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-c-
arboxylic acid
SYNTHESIS EXAMPLE 23
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole--
3-carbonyl]-amino}-3-o-tolyl-propionic acid
##STR00036##
[0609] 50 mg (0.1 mmol) of
(S)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-c-
arbonyl]-amino}-3-o-tolyl-propionic acid were dissolved in 5 ml of
DCM and 0.05 mmol of sodium borohydride were added. The mixture was
stirred at room temperature overnight. The solvent was removed in
vacuo and the residue subjected to preparative HPLC to given 52% of
the title compound.
SYNTHESIS EXAMPLE 24
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyraz-
ole-3-carbonyl]-amino}-3-o-tolyl-propionic acid and
(S)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyraz-
ole-3-carbonyl]-amino}-3-o-tolyl-propionic acid
##STR00037##
[0611] 100 mg of
(S)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-
-3-carbonyl]-amino}-3-o-tolyl-propionic acid were separated into
the two diastereomeric title compounds by HPLC on a chiral column
(Chiralpak AD-H/55, 250.times.4.6 mm) at 30.degree. C. (eluent:
heptane/ethanol/MOH (15:1:1)+0.1% TFA; flow: 1.0 ml/min). 45 mg of
the first diastereomer (retention time 16.35 min) eluted from the
column and 40 mg of the second diastereomer (retention time 21.15
min) eluted from the column were obtained, one of them being the
diastereomer with R configuration in the alcohol moiety and the
other of them being the diastereomer with S configuration in the
alcohol moiety (the stereochemistry in the alcohol moiety was not
determined; it was arbitrarily assigned R configuration in the
first diastereomer eluted from the column and S configuration in
the second diastereomer eluted from the column).
SYNTHESIS EXAMPLE 25
1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-car-
boxylic acid
##STR00038##
[0613] 610 mg (1.9 mmol) of
5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxyli-
c acid were dissolved in 20 ml of dry THF under argon and cooled to
0.degree. C. 1.4 ml of a 3 M solution of methylmagnesium bromide in
diethyl ether (4.2 mmol) were added over 10 min. The mixture was
allowed to reach room temperature overnight and then diluted with
50 ml of water and 30 ml of EA. After phase separation, the aqueous
phase was adjusted to pH=3 by addition of 1 M hydrochloric acid.
The precipitate which formed was dissolved by addition of 40 ml of
DCM, the organic phase was separated, dried over sodium sulfate and
evaporated. 390 mg (61%) of the title compound were obtained.
[0614] Analogously as described in synthesis example 25, the
following compounds were prepared, using ethylmagnesium bromide
instead of methylmagnesium bromide in the case of
5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic
acid:
1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-butoxy)-1H-pyrazole-3-car-
boxylic acid
1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-pyrazole-3-carboxyl-
ic acid
5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-car-
boxylic acid
5-(2-cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-car-
boxylic acid
SYNTHESIS EXAMPLE 26
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-py-
razole-3-carbonyl]-amino}-3-o-tolyl-propionic acid and
(S)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-py-
razole-3-carbonyl]-amino}-3-o-tolyl-propionic acid
##STR00039##
[0616] 390 mg (1.16 mmol) of
1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-ca-
rboxylic-acid were dissolved in 6 ml of DMF, 380 mg of TOTU (1.16
mmol) and 420 mg of NEM (3.6 mmol) were added and the mixture was
stirred for 5 min at room temperature. Then 208 mg (1.16 mmol) of
(S)-3-amino-3-(2-methyl-phenyl)-propionic acid were added and the
mixture was stirred overnight at room temperature. After
evaporation of the solvent, the residue was subjected to
preparative HPLC. 45 mg each of the two diastereomeric title
compounds were obtained, one of them being the diastereomer with R
configuration in the alcohol moiety and the other of them being the
diastereomer with S configuration in the alcohol moiety (the
stereochemistry in the alcohol moiety was not determined; it was
arbitrarily assigned R configuration in the first diastereomer
eluted from the column and S configuration in the second
diastereomer eluted from the column).
SYNTHESIS EXAMPLE 27
(S)-3-{[5-((R)-2-Cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyr-
azole-3-carbonyl]-amino}-3-o-tolyl-propionic acid and
(S)-3-{[5-((S)-2-cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyr-
azole-3-carbonyl]-amino}-3-o-tolyl-propionic acid
##STR00040##
[0618] 100 mg of
(S)-3-{[5-(2-cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazo-
le-3-carbonyl]-amino}-3-o-tolyl-propionic were separated into the
two diastereomeric title compounds by HPLC on a chiral column
(Chiralpak OJ-H/59, 250.times.4.6 mm) at 30.degree. C. (eluent:
heptane/ethanol (10:1)+0.1% TFA; flow: 1.0 ml/min). 40 mg each of
the two diastereomeric title compounds were obtained, one of them
being the diastereomer with R configuration in the alcohol moiety
and the other of them being the diastereomer with S configuration
in the alcohol moiety (the stereochemistry in the alcohol moiety
was not determined; it was arbitrarily assigned R configuration in
the first diastereomer (retention time 29.12 min) eluted from the
column and S configuration in the second diastereomer (retention
time 36.36 min) eluted from the column).
SYNTHESIS EXAMPLE 28
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid
[(S)-2-(1,1-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide
##STR00041##
[0620] 79.4 mg (0.2 mmol, 1 Eq) of
(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o--
tolyl-propionic acid are dissolved in 4 ml of DMF, 5Eq of
N-Ethylmorpholin and 1.1 Eq (0.22 mmol) of TOTU are added and the
resulting mixture is stirred for 10 minutes at RT. Then 0.22 mmol
of 1,1-Dimethyl-propylamine are added and the resulting mixture is
stirred overnight at RT.
[0621] 0.1 ml TFA was added, the mixture filtrated and subjected to
HPLC chromatography to yield 40 mg of the product. (Yield:
43%).
[0622] Analogously as described in the synthesis examples, the
example compounds of the formula I listed in Table 1 were
prepared.
TABLE-US-00001 TABLE 1 Example compounds of the formula I m/z Rt
LC/MS Activity Example Compound Name (1) (min) Method (2) 1
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 398.15 1.72 LC1 C
pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 2
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 318.15 2.87 LC3 C
carbonyl)-amino]-hexanoic acid 3
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.18 2.95 LC3 B
carbonyl)-amino]-3-(4-methoxy-phenyl)- propionic acid 4
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 304.13 2.70 LC3 C
carbonyl)-amino]-3-methyl-butyric acid 5
{1-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 330.15 2.87 LC3 C
carbonyl)-amino]-cyclopentyl}-acetic acid 6
3-(3-tert-Butoxy-phenyl)-3-[(5-hydroxy-1- 424.16 2.99 LC8 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 7
3-(3-tert-Butoxy-phenyl)-3-{[1-(2,5-dimethyl- 452.14 2.82 LC8 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 8
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 332.11 2.72 LC8 C
pyrazole-3-carbonyl]-amino}-3-methyl- butyric acid 9
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.12 2.74 LC8 B
carbonyl)-amino]-3-(3-methoxy-phenyl)- propionic acid 10
3-(3-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl- 386.06 2.88 LC8 B
1H-pyrazole-3-carbonyl)-amino]-propionic acid 11
3-(3,4-Dimethoxy-phenyl)-3-[(5-hydroxy-1- 412.13 2.61 LC8 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 12
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 436.06 3.09 LC8 B
carbonyl)-amino]-3-(4-trifluoromethoxy- phenyl)-propionic acid 13
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 318.12 2.64 LC8 C
carbonyl)-amino]-4-methyl-pentanoic acid 14
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 332.13 2.82 LC8 B
carbonyl)-amino]-heptanoic acid 15
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 380.12 2.92 LC8 C
carbonyl)-amino]-5-phenyl-pentanoic acid 16
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 353.1 2.06 LC8 B
carbonyl)-amino]-3-pyridin-3-yl-propionic acid 17
3-Cyclopropyl-3-[(5-hydroxy-1-phenyl-1H- 316.11 2.59 LC8 C
pyrazole-3-carbonyl)-amino]-propionic acid 18
3-Cyclohexyl-3-[(5-hydroxy-1-phenyl-1H- 358.14 2.95 LC8 B
pyrazole-3-carbonyl)-amino]-propionic acid 19
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 332.12 2.80 LC8 B
carbonyl)-amino]-5-methyl-hexanoic acid 20
3-(2-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl- 386.1 3.07 LC3 B
1H-pyrazole-3-carbonyl)-amino]-propionic acid 21
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.12 3.16 LC8 B
carbonyl)-amino]-3-o-tolyl-propionic acid 22
3-(4-Ethyl-phenyl)-3-[(5-hydroxy-1-phenyl- 380.13 2.98 LC8 B
1H-pyrazole-3-carbonyl)-amino]-propionic acid 23
3-(4-tert-Butoxy-phenyl)-3-[(5-hydroxy-1- 424.2 3.18 LC3 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 24
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 394.18 3.34 LC3 B
carbonyl)-amino]-3-(4-isopropyl-phenyl)- propionic acid 25
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 410.19 3.09 LC3 C
carbonyl)-amino]-3-(4-methoxy-2,3-dimethyl- phenyl)-propionic acid
26 3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 346.18 2.95 LC3 C
pyrazole-3-carbonyl]-amino}-hexanoic acid 27
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 410.18 3.04 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 28
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 410.12 2.86 LC8 C
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 29
3-(3-Chloro-phenyl)-3-{[1-(2,5-dimethyl- 414.07 2.97 LC8 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 30
3-(3,4-Dimethoxy-phenyl)-3-{[1-(2,5- 440.15 2.71 LC8 C
dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 31
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 464.06 3.12 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethoxy-phenyl)-propionic acid 32
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 346.12 2.77 LC8 C
pyrazole-3-carbonyl]-amino}-4-methyl- pentanoic acid 33
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 360.13 2.93 LC8 C
pyrazole-3-carbonyl]-amino}-heptanoic acid 34
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 408.13 3.02 LC8 C
pyrazole-3-carbonyl]-amino}-5-phenyl- pentanoic acid 35
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 381.11 2.19 LC8 C
pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 36
3-Cyclopropyl-3-{[1-(2,5-dimethyl-phenyl)-5- 344.12 2.69 LC8 C
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 37
3-Cyclohexyl-3-{[1-(2,5-dimethyl-phenyl)-5- 386.14 3.06 LC8 C
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 38
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 360.13 2.90 LC8 C
pyrazole-3-carbonyl]-amino}-5-methyl- hexanoic acid 39
3-(2-Chloro-phenyl)-3-{[1-(2,5-dimethyl- 414.06 2.93 LC8 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 40
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.13 2.93 LC8 B
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 41
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 408.14 3.07 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 42
(1-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 358.13 2.82 LC8 C
pyrazole-3-carbonyl]-amino}-cyclopentyl)- acetic acid 43
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 388.2 2.70 LC3 C
pyrazole-3-carbonyl]-amino}-3-(tetrahydro- pyran-4-yl)-propionic
acid 44 3-Cyclopentyl-3-{[1-(2,5-dimethyl-phenyl)-5- 372.12 2.93
LC3 C hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 45
3-(4-Chloro-phenyl)-3-{[1-(2,5-dimethyl- 414.16 3.22 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 46
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 436.27 3.65 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-isobutyl- phenyl)-propionic acid
47 3-(3,4-Difluoro-phenyl)-3-{[1-(2,5-dimethyl- 416.16 3.20 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 48
3-(3,4-Dichloro-phenyl)-3-{[1-(2,5-dimethyl- 448.13 3.43 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 49
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 398.19 3.09 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 50
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.22 3.18 LC3 C
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 51
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.21 3.17 LC3 C
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 52
3-(4-Cyano-phenyl)-3-{[1-(2,5-dimethyl- 405.2 3.00 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 53
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 448.17 3.32 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 54 3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 428.21 3.10 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-fluoro-4-
methoxy-phenyl)-propionic acid 55
3-Biphenyl-4-yl-3-{[1-(2,5-dimethyl-phenyl)- 456.23 3.50 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 56
3-(3,5-Difluoro-phenyl)-3-{[1-(2,5-dimethyl- 416.17 3.18 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 57
3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 448.17 3.39 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 58 3-(4-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl- 386.18 2.91 LC8
B 1H-pyrazole-3-carbonyl)-amino]-propionic acid 59
3-(3,5-Bis-trifluoromethyl-phenyl)-3-[(5- 488.15 3.21 LC8 C
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 60
3-(3,4-Difluoro-phenyl)-3-[(5-hydroxy-1- 388.19 2.83 LC8 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 61
3-(4-Fluoro-phenyl)-3-[(5-hydroxy-1-phenyl- 370.17 3.00 LC3 C
1H-pyrazole-3-carbonyl)-amino]-propionic acid 62
3-(3,4-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.15 3.03 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 63
3-(3-Fluoro-phenyl)-3-[(5-hydroxy-1-phenyl- 370.19 2.78 LC8 C
1H-pyrazole-3-carbonyl)-amino]-propionic acid 64
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.23 2.86 LC8 B
carbonyl)-amino]-3-p-tolyl-propionic acid 65
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.22 2.84 LC8 B
carbonyl)-amino]-3-m-tolyl-propionic acid 66
3-(4-tert-Butyl-phenyl)-3-[(5-hydroxy-1- 408.22 3.45 LC3 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 67
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.17 2.96 LC8 B
carbonyl)-amino]-3-(3-trifluoromethyl- phenyl)-propionic acid 68
3-(3-Fluoro-4-methoxy-phenyl)-3-[(5- 400.18 2.93 LC3 C
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 69
3-Biphenyl-4-yl-3-[(5-hydroxy-1-phenyl-1H- 428.21 3.37 LC3 B
pyrazole-3-carbonyl)-amino]-propionic acid 70
3-(3,5-Difluoro-phenyl)-3-[(5-hydroxy-1- 388.18 2.83 LC8 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 71
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.17 3.08 LC8 C
carbonyl)-amino]-3-(4-trifluoromethyl- phenyl)-propionic acid 72
3-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 422.1 3.07 LC8 C
1H-pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid
73 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 804.92 [(2M - H).sup.-]
4.22 LC2 C pyrazole-3-carbonyl]-amino}-3-(4-fluoro-
phenyl)-propionic acid 74 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H-
384.18 2.90 LC8 A pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic
acid 75 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 400.15 3.02 LC8 B
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 76
(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 384.18 2.87 LC8 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 77
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 400.15 2.78 LC8 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 78
3-{[1-(3,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.19 3.05 LC8 C
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 79
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 400.12 3.02 LC8 B
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 80
3-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 418.11 3.09 LC8 B
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 81
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 384.18 2.74 LC8 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 82
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.21 3.04 LC3 A
carbonyl)-amino]-3-o-tolyl-propionic acid 83
(R)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.24 3.02 LC3 C
carbonyl)-amino]-3-o-tolyl-propionic acid 84
3-(2,4-Dimethyl-phenyl)-3-[(5-hydroxy-1- 380.21 3.89 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 85
3-(4-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy- 384.12 3.09 LC3 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 86
3-(2,4-Difluoro-phenyl)-3-{[1-(4-fluoro- 406.06 2.87 LC8 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 87
(S)-3-{[5-Hydroxy-1-(4-methoxy-phenyl)-1H- 396.12 2.83 LC8 B
pyrazole-3-carbonyl]-amino}-3-o-tolyl-
propionic acid 88 3-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy-
452.06 3.04 LC8 C 1H-pyrazole-3-carbonyl]-amino}-3-(2-fluoro-
4-methoxy-phenyl)-propionic acid 89
3-(2,4-Dimethyl-phenyl)-3-{[1-(4-fluoro- 398.12 3.02 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 90
3-(2-Fluoro-4-methoxy-phenyl)-3-{[1-(4- 418.1 2.87 LC8 C
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 91 3-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 432.1 3.20 LC8
C 1H-pyrazole-3-carbonyl]-amino}-3-(2,4- dimethyl-phenyl)-propionic
acid 92 3-(2-Fluoro-4-methoxy-phenyl)-3-[(5- 400.1 2.81 LC8 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 93
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 398.18 3.08 LC8
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid methyl ester
94 (S)-3-{[5-Hydroxy-1-(3-methoxy-phenyl)-1H- 396.12 2.87 LC8 B
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 95
(S)-3-(2,4-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.02 3.06 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 96
(S)-3-(2-Fluoro-phenyl)-3-[(5-hydroxy-1- 370.08 2.80 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 97
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.06 2.96 LC8 B
carbonyl)-amino]-3-(2-trifluoromethyl- phenyl)-propionic acid 98
(S)-3-(4-Chloro-phenyl)-3-[(5-hydroxy-1- 386.06 2.95 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 99
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.09 3.04 LC8 B
carbonyl)-amino]-3-(4-trifluoromethyl- phenyl)-propionic acid 100
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.12 2.85 LC8 B
carbonyl)-amino]-3-(2-methoxy-phenyl)- propionic acid 101
(S)-3-(4-Cyano-phenyl)-3-[(5-hydroxy-1- 377.1 2.71 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 102
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 444.1 3.16 LC8 B
carbonyl)-amino]-3-(4-phenoxy-phenyl)- propionic acid 103
(S)-3-(2,6-Difluoro-phenyl)-3-[(5-hydroxy-1- 388.09 2.83 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 104
3-(4'-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 446.13 3.17 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 105
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 418.11 2.30 LC8 C
carbonyl)-amino]-3-(4-imidazol-1-yl-phenyl)- propionic acid 106
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.01 3.06 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dichloro- phenyl)-propionic acid
107 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.05 2.78 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 108
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.02 2.91 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 109 (S)-3-(4-Chloro-phenyl)-3-{[1-(2-chloro- 420.03 2.91 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
110 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.05 3.00 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 111 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.03 [(M -
H).sup.-] 3.90 LC2 B pyrazole-3-carbonyl]-amino}-3-(2-methoxy-
phenyl)-propionic acid 112
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 411.06 2.67 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 113
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 478.08 3.12 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
114 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 422.03 2.79 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2,6-difluoro- phenyl)-propionic acid
115 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.08 3.14 LC8 A
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro- biphenyl-4-yl)-propionic
acid 116 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 452.07 2.23 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-imidazol-1- yl-phenyl)-propionic
acid 117 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 438 3.40 LC8
B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
118 (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 388.11 2.96 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
119 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.05 2.93 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 120 (S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 404.06 2.86 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
121 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.04 2.98 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 122 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 400.14 2.77 LC8
B pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
123 (S)-3-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 395.1 2.64 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
124 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 462.11 3.08 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
125 (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 406.06 2.97 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
126 3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 464.13 3.14 LC8 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
127 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 436.1 2.22 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-imidazol-1- yl-phenyl)-propionic
acid 128 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 412.21 3.40 LC3
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid ethyl ester
129 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 398.18 2.99 LC8 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 130
(S)-3-{[1-(5-Chloro-pyridin-2-yl)-5-hydroxy- 401.13 3.01 LC8 C
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 131
(S)-3-{[1-(2-Chloro-pyridin-4-yl)-5-hydroxy- 401.15 3.07 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 132
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.12 2.79 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-4-
methoxy-phenyl)-propionic acid 133
3-(2-Fluoro-4-methoxy-phenyl)-3-{[1-(2- 418.14 2.73 LC8 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 134 3-(4-Ethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5- 398.19 3.17
LC3 B hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 135
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 400.16 3.05 LC3 B
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 136
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 401.18 2.60 LC3 B
pyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic
acid 137 (S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 353.15 2.14 LC8
B carbonyl)-amino]-3-pyridin-3-yl-propionic acid 138
(S)-3-{[5-Hydroxy-1-(4-trifluoromethyl- 436.17 2.78 LC8 C
pyrimidin-2-yl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 139 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 417.13 2.67 LC8
B pyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic
acid 140 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 371.16 2.00 LC3
B pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 141
(S)-3-[(5-Hydroxy-1-pyridin-4-yl-1H- 367.19 2.18 LC3 C
pyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 142
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.15 3.04 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic
acid 143 (S)-3-[(5-Hydroxy-1-pyridin-3-yl-1H- 367.18 2.25 LC8 C
pyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 144
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 383.17 2.46 LC8 B
carbonyl)-amino]-3-(6-methoxy-pyridin-3-yl)- propionic acid 145
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 387.12 2.08 LC8 B
pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 146
(S)-3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(2- 464.07 3.08 LC8 C
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 147 (R)-3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(2- 464.07 3.07 LC8
A fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 148
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.05 3.25 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro- biphenyl-4-yl)-propionic
acid 149 (R)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.05 3.11 LC8
A pyrazole-3-carbonyl]-amino}-3-(4'-fluoro-
biphenyl-4-yl)-propionic acid 150
3-Biphenyl-4-yl-3-{[1-(2-fluoro-phenyl)-5- 446.16 3.05 LC8 A
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 151
3-Biphenyl-4-yl-3-[(5-hydroxy-1-pyridin-4-yl- 429.16 2.63 LC8 C
1H-pyrazole-3-carbonyl)-amino]-propionic acid 152
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 506.12 3.63 LC8
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
ethyl ester 153 3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 492.12
3.47 LC8 phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
amino}-propionic acid ethyl ester 154
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 508.1 3.51 LC8
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro- biphenyl-4-yl)-propionic
acid ethyl ester 155 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 490.14
3.49 LC8 pyrazole-3-carbonyl]-amino}-3-(4-phenoxy-
phenyl)-propionic acid ethyl ester 156
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 476.14 3.03 LC8 B
pyrazole-3-carbonyl]-amino}-3-(3'-methoxy- biphenyl-4-yl)-propionic
acid 157 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 492.12 3.09 LC8 B
pyrazole-3-carbonyl]-amino}-3-(3'-methoxy- biphenyl-4-yl)-propionic
acid 158 3-Benzo[1,3]dioxol-4-yl-3-[(5-hydroxy-1- 396.18 2.95 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 159
(S)-3-(2-Bromo-phenyl)-3-[(5-hydroxy-1- 430.11 3.09 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 160
(S)-3-(3-Cyano-phenyl)-3-[(5-hydroxy-1- 377.18 2.87 LC3 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 161
3-(2,4-Dimethoxy-phenyl)-3-[(5-hydroxy-1- 412.21 3.05 LC3 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 162
3-(2-Chloro-4-methoxy-phenyl)-3-[(5- 416.18 3.10 LC3 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 163
(S)-3-(4-Fluoro-phenyl)-3-[(5-hydroxy-1- 370.18 3.00 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 164
(S)-3-(2,3-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.11 3.22 LC3 A
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 165
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.19 2.93 LC3 C
carbonyl)-amino]-3-(3-methoxy-phenyl)- propionic acid 166
(S)-3-(3-Fluoro-phenyl)-3-[(5-hydroxy-1- 370.17 3.04 LC3 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 167
(S)-3-(3-Chloro-phenyl)-3-[(5-hydroxy-1- 386.15 3.10 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 168
3-(2,3-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.11 3.22 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 169
(2R,3R)-2-Hydroxy-3-[(5-hydroxy-1-phenyl- 398.2 2.79 LC3 C
1H-pyrazole-3-carbonyl)-amino]-3-(2- methoxy-phenyl)-propionic acid
170 (S)-3-(2,3-Dimethoxy-phenyl)-3-[(5-hydroxy- 412.21 2.99 LC3 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid
171 3-(3'-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 446.22 3.43 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 172
3-(3-Chloro-2-fluoro-phenyl)-3-[(5-hydroxy- 404.14 3.18 LC3 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 173
3-[3-(4-Chloro-phenoxy)-phenyl]-3-[(5- 478.18 3.54 LC3 C
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 174
3-Benzo[1,3]dioxol-4-yl-3-{[1-(2,4-difluoro- 432.19 2.95 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
175 (S)-3-(2-Bromo-phenyl)-3-{[1-(2,4-difluoro- 466.1 3.07 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
176 (S)-3-(4-Cyano-phenyl)-3-{[1-(2,4-difluoro- 413.17 2.85 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
177 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 418.17 3.00 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(2- methoxy-phenyl)-propionic acid
178 3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(2,4- 452.16 3.22 LC3 C
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 179
3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(2,4- 452.17 3.09 LC3 B
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 180
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 406.17 2.97 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid
181 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2,4- 456.11 3.20 LC3 A
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 182
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 418.18 2.95 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(3- methoxy-phenyl)-propionic acid
183 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 406.14 3.04 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid
184 (S)-3-(3-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.14 3.12 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
185 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 456.16 3.24 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethyl-phenyl)-propionic acid 186
3-(2,3-Dichloro-phenyl)-3-{[1-(2,4-difluoro- 456.11 3.18 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
187 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 472.16 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethoxy-phenyl)-propionic acid 188
(2R,3R)-3-{[1-(2,4-Difluoro-phenyl)-5- 434.17 2.79 LC3 C
hydroxy-1H-pyrazole-3-carbonyl]-amino}-2-
hydroxy-3-(2-methoxy-phenyl)-propionic acid 189
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 448.21 3.04 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic
acid 190 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 402.19 3.05 LC3
B 1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 191
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 416.2 3.14 LC3 A
pyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid
192 3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(2,4- 440.11 3.18 LC3 B
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 193
3-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 490.13 3.30 LC3 B
(2,4-difluoro-phenyl)-5-hydroxy-1H-pyrazole-
3-carbonyl]-amino}-propionic acid 194
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 416.21 3.24 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 195
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 416.21 3.18 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid
196 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 420.18 3.07 LC3 A
pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic
acid 197 3-Biphenyl-4-yl-3-{[1-(2,4-difluoro-phenyl)-5- 464.22 3.39
LC3 B hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 198
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 456.14 3.15 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(2-
trifluoromethyl-phenyl)-propionic acid 199
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 480.21 3.37 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
200 (S)-3-(4-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.14 3.12 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
201 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2,4- 456.11 3.25 LC3 B
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 202
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 482.22 3.42 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro- biphenyl-4-yl)-propionic
acid 203 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 430.18 2.99 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 204
(S)-3-(2-Bromo-phenyl)-3-{[1-(2-chloro- 464.04 3.05 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
205 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 411.12 2.84 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-cyano- phenyl)-propionic acid 206
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.12 3.17 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 207 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 446.18 3.00 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4- dimethoxy-phenyl)-propionic
acid 208 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.11 2.97 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 209
3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(2- 450.11 3.14 LC3 B
chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 210 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(2- 450.15 3.05 LC3 B
chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 211 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.12 2.99 LC3
B pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid
212 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.06 3.17 LC3 A
pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid
213 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 416.15 2.90 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
214 (S)-3-(3-Chloro-phenyl)-3-{[1-(2-chloro- 420.09 3.07 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
215 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 470.12 3.32 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethoxy-phenyl)-propionic acid 216
(2R,3R)-3-{[1-(2-Chloro-phenyl)-5-hydroxy- 432.13 2.74 LC3 C
1H-pyrazole-3-carbonyl]-amino}-2-hydroxy-
3-(2-methoxy-phenyl)-propionic acid 217
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 400.15 3.02 LC3 B
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 218
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.12 3.20 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 219 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.19 3.40 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3'-fluoro- biphenyl-4-yl)-propionic
acid 220 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.18 3.12 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid
221 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 472.14 3.22 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-
trifluoromethyl-phenyl)-propionic acid 222
3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(2-chloro- 438.08 3.10 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
223 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 488.08 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-chloro-3-
trifluoromethyl-phenyl)-propionic acid 224
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.16 3.18 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 225
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.16 3.12 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid
226 3-Biphenyl-4-yl-3-{[1-(2-chloro-phenyl)-5- 462.2 3.39 LC3 B
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 227
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.06 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3,4-dichloro- phenyl)-propionic acid
228 3-Benzo[1,3]dioxol-4-yl-3-{[1-(2-fluoro- 414.16 2.89 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
229 3-(3-Benzyloxy-phenyl)-3-{[1-(2-fluoro- 476.21 3.32 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
230 (S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 395.15 2.77 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
231 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.14 3.14 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 232 3-(2,4-Dimethoxy-phenyl)-3-{[1-(2-fluoro- 430.2 2.97 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
233 3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)- 388.14 2.87 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 234
3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(2- 434.14 3.07 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 235 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(2- 434.17 3.05 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 236 (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 388.16 2.90 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
237 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 400.18 2.85 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
238 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 456.16 3.22 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-4-
trifluoromethyl-phenyl)-propionic acid 239
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 454.17 3.24 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethoxy-phenyl)-propionic acid 240
(2R,3R)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy- 416.17 2.72 LC3 C
1H-pyrazole-3-carbonyl]-amino}-2-hydroxy-
3-(2-methoxy-phenyl)-propionic acid 241
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.14 3.17 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 242 3-(3'-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 464.22 3.35
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 243 3-(4-Chloro-2-fluoro-phenyl)-3-{[1-(2-fluoro- 422.13 3.09
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 244 3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(2-fluoro- 422.11 3.04
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 245 3-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 472.11 3.22
LC3 B (2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 246
3-[3-(4-Chloro-phenoxy)-phenyl]-3-{[1-(2- 496.16 3.50 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 247 3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 398.2 3.09 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
248 3-(4-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 402.18 3.02 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
249 3-Benzo[1,3]dioxol-4-yl-3-{[1-(3-chloro- 430.14 3.24 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
250 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 430.19 3.24 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 251
(S)-3-(2-Bromo-phenyl)-3-{[1-(3-chloro- 464.07 3.30 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
252 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 411.14 3.12 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-cyano- phenyl)-propionic acid 253
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 416.16 3.25 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
254 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.13 3.20 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 255
3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(3- 450.13 3.42 LC3 B
chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 256 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.13 3.43 LC3
C pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethyl-phenyl)-propionic acid 257
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.09 3.43 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid
258 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 400.17 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 259
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.13 3.45 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 260 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 480.19 3.62 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3'-fluoro- biphenyl-4-yl)-propionic
acid 261 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 414.18 3.39 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid
262 3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(3-chloro- 438.1 3.37 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
263 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 488.09 3.49 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-chloro-3-
trifluoromethyl-phenyl)-propionic acid 264
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 414.18 3.43 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 265
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 422.14 3.24 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,6-difluoro- phenyl)-propionic acid
266 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.09 3.52 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dichloro- phenyl)-propionic acid
267 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 480.16 3.65 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro- biphenyl-4-yl)-propionic
acid 268 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 387.13 2.37 LC3
C pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 269
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 417.13 2.87 LC3 C
pyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic
acid 270 (S)-3-(2-Bromo-phenyl)-3-{[1-(4-chloro- 464.05 3.30 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
271 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 411.12 3.15 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-cyano- phenyl)-propionic acid 272
(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 411.13 3.10 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 273
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 446.16 3.29 LC3 C
pyrazole-3-carbonyl]-amino}-3-(2,4- dimethoxy-phenyl)-propionic
acid 274 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 416.14 3.27 LC3
C pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
275 3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(4- 450.11 3.45 LC3 C
chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 276 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 404.13 3.22 LC3
C pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid
277 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.06 3.49 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid
278 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 416.15 3.18 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
279 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 404.12 3.24 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 280
(S)-3-(3-Chloro-phenyl)-3-{[1-(4-chloro- 420.1 3.35 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
281 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.07 3.42 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid
282 (2R,3R)-3-{[1-(4-Chloro-phenyl)-5-hydroxy- 432.15 3.04 LC3 C
1H-pyrazole-3-carbonyl]-amino}-2-hydroxy-
3-(2-methoxy-phenyl)-propionic acid 283
(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 446.17 3.22 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic
acid 284 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 400.15 3.30 LC3
B pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 285
(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.12 3.43 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 286 3-(4-Chloro-2-fluoro-phenyl)-3-{[1-(4-chloro- 438.1 3.40
LC3 C phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 287 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 414.17 3.43 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid
288 3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(4-chloro- 438.1 3.42 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
289 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 488.09 3.50 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-chloro-3-
trifluoromethyl-phenyl)-propionic acid 290
3-[3-(4-Chloro-phenoxy)-phenyl]-3-{[1-(4- 512.14 3.77 LC3 C
chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 291 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 414.17 3.40 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid
292 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 418.15 3.37 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic
acid 293 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 404.13 3.25 LC3
C pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid
294 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 478.18 3.60 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
295 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 422.12 3.25 LC3 C
pyrazole-3-carbonyl]-amino}-3-(2,6-difluoro- phenyl)-propionic acid
296 (S)-3-(4-Chloro-phenyl)-3-{[1-(4-chloro- 420.11 3.37 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
297 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.07 3.49 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dichloro- phenyl)-propionic acid
298 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 387.14 2.42 LC3 C
pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 299
(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 417.14 2.92 LC3 C
pyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic
acid 300 3-Benzo[1,3]dioxol-4-yl-3-{[1-(3-fluoro- 414.16 3.07 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
301 3-(3-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)- 404.13 3.24 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 302
(S)-3-(2-Bromo-phenyl)-3-{[1-(3-fluoro- 448.08 3.17 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
303 (S)-3-(3-Cyano-phenyl)-3-{[1-(3-fluoro- 395.16 3.02 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
304 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 305 (S)-3-(4-Cyano-phenyl)-3-{[1-(3-fluoro- 395.17 2.97 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
306 3-(2,4-Dimethoxy-phenyl)-3-{[1-(3-fluoro- 430.19 3.14 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
307 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 400.18 3.12 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
308 3-(2-Fluoro-phenyl)-3-{[1-(3-fluoro-phenyl)- 388.15 3.05 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 309
3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(3- 434.15 3.32 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 310 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(3- 434.17 3.18 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 311 (S)-3-(4-Fluoro-phenyl)-3-{[1-(3-fluoro- 388.16 3.10 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
312 (S)-3-(3-Fluoro-phenyl)-3-{[1-(3-fluoro- 388.16 3.10 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
313 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.34 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 314 3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.1 3.30 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
315 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 454.16 3.43 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-
trifluoromethoxy-phenyl)-propionic acid 316
(2R,3R)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy- 416.18 2.89 LC3 C
1H-pyrazole-3-carbonyl]-amino}-2-hydroxy-
3-(2-methoxy-phenyl)-propionic acid 317
(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 384.19 3.17 LC3 B
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 318
(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.32 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 319 3-(3'-Fluoro-biphenyl-4-yl)-3-{[1-(3-fluoro- 464.22 3.52
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 320 3-(4-Chloro-2-fluoro-phenyl)-3-{[1-(3-fluoro- 422.13 3.29
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 321 3-(2,5-Dimethyl-phenyl)-3-{[1-(3-fluoro- 398.21 3.25 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
322 3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(3-fluoro- 422.13 3.29 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
323 3-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 472.12 3.39 LC3 B
(3-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 324
3-(4-Ethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5- 398.2 3.32 LC3 B
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 325
3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro- 398.2 3.27 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
326 3-(4-Fluoro-2-methyl-phenyl)-3-{[1-(3-fluoro- 402.18 3.24 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
327 3-Biphenyl-4-yl-3-{[1-(3-fluoro-phenyl)-5- 446.23 3.42 LC3 B
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 328
3-(3,4-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.11 3.39 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
329 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.25 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 330 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 462.21 3.49 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
331 (S)-3-(4-Chloro-phenyl)-3-{[1-(3-fluoro- 404.14 3.24 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
332 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.1 3.35 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
333 3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(3-fluoro- 464.23 3.49 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
334 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 371.17 2.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 335
(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 401.17 2.72 LC3 B
pyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic
acid 336 3-Benzo[1,3]dioxol-4-yl-3-{[1-(4-fluoro- 414.17 3.04 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
337 3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 414.21 3.10 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid
338 3-(3-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)- 404.13 3.17 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 339
(S)-3-(2-Bromo-phenyl)-3-{[1-(4-fluoro- 448.09 3.18 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
340 (S)-3-(3-Cyano-phenyl)-3-{[1-(4-fluoro- 395.17 2.93 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
341 (S)-3-(4-Cyano-phenyl)-3-{[1-(4-fluoro- 395.17 2.93 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
342 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 400.19 3.07 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
343 3-(2-Fluoro-phenyl)-3-{[1-(4-fluoro-phenyl)- 388.16 3.07 LC3 C
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 344
3-(5-Chloro-2-methoxy-phenyl)-3-{[1-(4- 434.15 3.24 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 345 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(4- 434.17 3.20 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 346 (S)-3-(4-Fluoro-phenyl)-3-{[1-(4-fluoro- 388.16 3.10 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
347 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.1 3.27 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
348 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 400.19 3.02 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
349 (S)-3-(3-Fluoro-phenyl)-3-{[1-(4-fluoro- 388.16 3.07 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
350 (S)-3-(3-Chloro-phenyl)-3-{[1-(4-fluoro- 404.14 3.18 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
351 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.34 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 352 3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.11 3.27 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
353 (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(4-fluoro- 430.2 3.05 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
354 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 384.19 3.14 LC3 B
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 355
(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 438.16 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic
acid 356 3-(3'-Fluoro-biphenyl-4-yl)-3-{[1-(4-fluoro- 464.21 3.47
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 357 3-(4-Chloro-2-fluoro-phenyl)-3-{[1-(4-fluoro- 422.13 3.22
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 358 3-(2,3-Dimethyl-phenyl)-3-{[1-(4-fluoro- 398.21 3.22 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
359 3-(2,5-Dimethyl-phenyl)-3-{[1-(4-fluoro- 398.21 3.27 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
360 3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 456.16 3.35 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-
trifluoromethyl-phenyl)-propionic acid 361
3-(3-Chloro-2-fluoro-phenyl)-3-{[1-(4-fluoro- 422.13 3.20 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
362 3-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 472.13 3.35 LC3 B
(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 363
3-(4-Ethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5- 398.2 3.27 LC3 B
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 364
3-(4-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro- 402.19 3.17 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
365 3-Biphenyl-4-yl-3-{[1-(4-fluoro-phenyl)-5- 446.22 3.42 LC3 B
hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 366
(S)-3-(2-Fluoro-phenyl)-3-{[1-(4-fluoro- 388.16 3.04 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
367 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 438.16 3.22 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 368 (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(4-fluoro- 406.15 3.07
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 369 (S)-3-(4-Chloro-phenyl)-3-{[1-(4-fluoro- 404.14 3.18 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
370 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.11 3.39 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
371 3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(4-fluoro- 464.22 3.47 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
372 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 371.17 2.22 LC3 C
pyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 373
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 396.22 3.05 LC3 B
carbonyl)-amino]-3-(4-methoxy-2-methyl- phenyl)-propionic acid 374
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.21 2.93 LC3 B
carbonyl)-amino]-3-(4-methoxy-phenyl)- propionic acid 375
3-(5-Chloro-2-methoxy-phenyl)-3-[(5- 416.16 3.24 LC3 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 376
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.19 3.07 LC3 B
carbonyl)-amino]-3-m-tolyl-propionic acid 377
3-(2,3-Dimethyl-phenyl)-3-[(5-hydroxy-1- 380.21 3.15 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 378
3-(2,5-Dimethyl-phenyl)-3-[(5-hydroxy-1- 380.21 3.22 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 379
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 432.22 2.99 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 380
3-(3-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.15 3.14 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
381 (S)-3-(3-Cyano-phenyl)-3-{[1-(2,4-difluoro- 413.17 2.87 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
382 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 418.19 2.93 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(4- methoxy-phenyl)-propionic acid
383 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 448.21 3.00 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4- dimethoxy-phenyl)-propionic
acid 384 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 482.21 3.42 LC3
B pyrazole-3-carbonyl]-amino}-3-(3'-fluoro-
biphenyl-4-yl)-propionic acid 385
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 474.17 3.25 LC3 A
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-
trifluoromethyl-phenyl)-propionic acid 386
3-[3-(4-Chloro-phenoxy)-phenyl]-3-{[1-(2,4- 514.16 3.60 LC3 B
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 387
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 406.15 2.97 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid
388 (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2,4- 424.15 3.02 LC3 B
difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 389
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 389.18 2.12 LC3 C
1H-pyrazole-3-carbonyl]-amino}-3-pyridin-3- yl-propionic acid 390
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 419.19 2.60 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-(6-
methoxy-pyridin-3-yl)-propionic acid 391
3-(3-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)- 420.1 3.12 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 392
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 416.17 2.90 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
393 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.13 2.99 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 394
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 446.17 2.97 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic
acid 395 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 414.21 2.93 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 396
3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)- 404.13 3.04 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 397
(S)-3-(2-Bromo-phenyl)-3-{[1-(2-fluoro- 448.08 3.05 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
398 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 400.18 2.89 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
399 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.09 3.18 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
400 (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 388.16 2.90 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
401 (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 404.12 3.02 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
402 3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.09 3.15 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
403 (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro- 430.19 2.93 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
404 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 384.17 2.95 LC3 B
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 405
3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro- 398.21 3.07 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
406 3-(2,5-Dimethyl-phenyl)-3-{[1-(2-fluoro- 398.2 3.14 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
407 3-(3,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.09 3.17 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
408 3-(3-Chloro-phenyl)-3-{[1-(3-chloro-phenyl)- 420.11 3.37 LC3 B
5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 409
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 416.16 3.14 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
410 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 411.15 3.15 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 411
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.14 3.22 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 412
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.08 3.42 LC3 C
pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid
413 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 416.16 3.22 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
414 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.14 3.20 LC3 C
pyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 415
(S)-3-(3-Chloro-phenyl)-3-{[1-(3-chloro- 420.11 3.39 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
416 (2R,3R)-3-{[1-(3-Chloro-phenyl)-5-hydroxy- 432.15 3.02 LC3 C
1H-pyrazole-3-carbonyl]-amino}-2-hydroxy-
3-(2-methoxy-phenyl)-propionic acid 417
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 446.17 3.25 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic
acid 418 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 472.15 3.45 LC3 C
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-
trifluoromethyl-phenyl)-propionic acid 419
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 414.19 3.39 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid
420 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 418.16 3.35 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic
acid 421 3-Biphenyl-4-yl-3-{[1-(3-chloro-phenyl)-5- 462.2 3.59 LC3
B hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid
422 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.12 3.18 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 423
(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 416.15 3.22 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
424 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(4- 450.14 3.37 LC3 B
chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 425 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 480.2 3.68 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro- biphenyl-4-yl)-propionic
acid 426 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 414.2 3.12 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 427
(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 400.19 3.07 LC3 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
428 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.1 3.37 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
429 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 400.18 3.05 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
430 (S)-3-(3-Chloro-phenyl)-3-{[1-(3-fluoro- 404.13 3.24 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
431 (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(3-fluoro- 430.2 3.09 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
432 3-(2,3-Dimethyl-phenyl)-3-{[1-(3-fluoro- 398.21 3.30 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
433 (S)-3-(2-Fluoro-phenyl)-3-{[1-(3-fluoro- 388.16 3.12 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
434 (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(3-fluoro- 406.15 3.10 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
435 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 400.2 2.99 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
436 3-(2,4-Dimethoxy-phenyl)-3-{[1-(4-fluoro- 430.21 3.09 LC3 C
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
437 3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 462.22 3.47 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid
438 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 401.18 2.70 LC3 B
pyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic
acid 439 3-Biphenyl-4-yl-3-{[1-(2-chloro-pyridin-4-yl)- 463.13 3.06
LC8 B 5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 440
3-Biphenyl-4-yl-3-[(5-hydroxy-1-pyridin-3-yl- 429.17 2.66 LC8 C
1H-pyrazole-3-carbonyl)-amino]-propionic acid 441
3-(2-Fluoro-6-methoxy-phenyl)-3-[(5- 400.19 3.04 LC3 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 442
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 444.23 3.42 LC3 C
carbonyl)-amino]-3-(2-phenoxy-phenyl)- propionic acid 443
3-(5-Fluoro-2-trifluoromethyl-phenyl)-3-[(5- 438.14 3.25 LC3 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 444
3-(2,5-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.11 3.22 LC3 A
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 445
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.2 3.09 LC3 B
carbonyl)-amino]-3-p-tolyl-propionic acid 446
(S)-3-(2-Chloro-phenyl)-3-[(5-hydroxy-1- 386.15 3.02 LC3 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 447
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 420.18 3.07 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic
acid 448 3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 465.2 2.89 LC3
B (2,4-difluoro-phenyl)-5-hydroxy-1H-pyrazole-
3-carbonyl]-amino}-propionic acid 449
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 436.19 3.04 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-6-
methoxy-phenyl)-propionic acid 450
3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 468.14 3.20 LC3 B
(2,4-difluoro-phenyl)-5-hydroxy-1H-pyrazole-
3-carbonyl]-amino}-propionic acid 451
3-(2,5-Difluoro-phenyl)-3-{[1-(2,4-difluoro- 424.16 2.99 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
452 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 474.14 3.37 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
trifluoromethyl-phenyl)-propionic acid 453
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 436.17 3.04 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
methoxy-phenyl)-propionic acid 454
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 402.18 3.04 LC3 B
1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 455
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.15 3.04 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic
acid 456 3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 463.17 2.90 LC3
C (2-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid; compound with trifluoro-acetic
acid 457 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.17 3.02 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-6-
methoxy-phenyl)-propionic acid 458
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-chloro- 438.1 3.09 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
459 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 422.15 2.97 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,5-difluoro- phenyl)-propionic acid
460 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 472.16 3.18 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
trifluoromethyl-phenyl)-propionic acid 461
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.16 3.10 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2- methyl-phenyl)-propionic
acid 462 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.1 3.17 LC3 A
pyrazole-3-carbonyl]-amino}-3-(2,5-dichloro- phenyl)-propionic acid
463 3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 461.24 [(M -
H).sup.-] 4.39 LC4 C (3-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 464
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 466.14 3.40 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,2-difluoro-
benzo[1,3]dioxol-4-yl)-propionic acid 465
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 422.14 3.29 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,5-difluoro- phenyl)-propionic acid
466 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 472.16 3.42 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
trifluoromethyl-phenyl)-propionic acid 467
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 486.13 3.50 LC3 C
pyrazole-3-carbonyl]-amino}-3-(2-
trifluoromethylsulfanyl-phenyl)-propionic acid 468
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 418.19 3.32 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic
acid 469 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 434.17 3.32 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-6-
methoxy-phenyl)-propionic acid 470
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-chloro- 438.11 3.32 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
471 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 466.13 3.40 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,2-difluoro-
benzo[1,3]dioxol-4-yl)-propionic acid 472
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 422.14 3.25 LC3 C
pyrazole-3-carbonyl]-amino}-3-(2,5-difluoro- phenyl)-propionic acid
473 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 472.13 3.42 LC3 C
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
trifluoromethyl-phenyl)-propionic acid 474
(S)-3-(2-Chloro-phenyl)-3-{[1-(4-chloro- 420.12 3.27 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
475 3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-fluoro- 422.15 3.00 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
476 3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 450.15 3.22 LC3 B
(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 477
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 456.17 3.12 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
trifluoromethyl-phenyl)-propionic acid 478
3-(5-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 402.19 3.02 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
479 3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.12 3.14 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
480 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 384.21 2.97 LC3 B
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 481
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 445.34 [(M - H).sup.-] 2.87
LC4 B pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2-
yl-phenyl)-propionic acid 482
3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(3-fluoro- 402.2 3.18 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
483 3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(3-fluoro- 422.14 3.22 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
484 3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 450.18 3.27 LC3 B
(3-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 485
3-(2,5-Difluoro-phenyl)-3-{[1-(3-fluoro- 406.17 3.10 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
486 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 456.17 3.49 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
trifluoromethyl-phenyl)-propionic acid 487
3-(5-Fluoro-2-methyl-phenyl)-3-{[1-(3-fluoro- 402.19 3.18 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
488 3-(2,5-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.12 3.32 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
489 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 384.21 3.20 LC3 B
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 490
3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 447.22 2.95 LC3 C
(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 491
3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 450.16 3.24 LC3 B
(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 492
3-(5-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro- 402.19 3.22 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
493 3-(2,5-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.08 3.29 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
494 3-(3-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy- 384.19 3.14 LC3 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 495
3-(2-Chloro-5-fluoro-phenyl)-3-[(5-hydroxy- 404.13 3.12 LC3 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 496
3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-[(5- 432.14 3.20 LC3 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 497
3-(5-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy- 384.2 3.09 LC3 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 498
3-(5-Fluoro-2-methoxy-phenyl)-3-[(5- 400.18 3.10 LC3 B
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 499
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 429.22 2.39 LC3 B
carbonyl)-amino]-3-(4-pyridin-2-yl-phenyl)- propionic acid;
compound with trifluoro- acetic acid 500
3-(2,5-Dichloro-phenyl)-3-{[1-(2,4-difluoro- 456.1 3.18 LC3 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
501 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 465.21 2.40 LC3 A
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid; compound with trifluoro-acetic acid 502
(S)-3-(2-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.12 3.14 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
503 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 466.11 3.17 LC3 B
pyrazole-3-carbonyl]-amino}-3-(2,2-difluoro-
benzo[1,3]dioxol-4-yl)-propionic acid 504
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.16 3.00 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-
methoxy-phenyl)-propionic acid 505
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 469.29 [(M - H).sup.-] 2.85
LC4 C pyrazole-3-carbonyl]-amino}-3-(4-morpholin-
4-yl-phenyl)-propionic acid 506
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 463.21 2.39 LC3 A
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid 507 (S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro- 420.12 3.17 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
508 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 418.17 3.32 LC3 B
pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic
acid 509 3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(3-chloro- 438.12 3.34
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 510 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 418.17 3.32 LC3 B
pyrazole-3-carbonyl]-amino}-3-(5-fluoro-2- methyl-phenyl)-propionic
acid 511 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.05 [(M -
H).sup.-] 4.47 LC4 B pyrazole-3-carbonyl]-amino}-3-(2,5-dichloro-
phenyl)-propionic acid 512
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 400.18 3.30 LC3 B
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 513
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 463.2 2.59 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid 514 (S)-3-(2-Chloro-phenyl)-3-{[1-(3-chloro- 420.13 3.32 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
515 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 463.19 2.59 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid 516 3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 402.19 3.00
LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 517 3-(2,5-Difluoro-phenyl)-3-{[1-(2-fluoro- 406.16 2.90 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
518 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 453.32 [(M - H).sup.-]
3.26 LC4 C pyrazole-3-carbonyl]-amino}-3-(4-morpholin-
4-yl-phenyl)-propionic acid 519
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 404.14 2.95 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
520 3-(5-Fluoro-2-methoxy-phenyl)-3-{[1-(3- 418.19 3.17 LC3 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 521 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 447.24 2.50 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid 522 (S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro- 404.15 3.32 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
523 3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro- 402.2 3.17 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
524 3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-fluoro- 422.14 3.20 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
525 3-(5-Fluoro-2-methoxy-phenyl)-3-{[1-(4- 418.16 3.17 LC3 C
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 526 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 384.17 3.15 LC3
B pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 527
3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 447.19 2.45 LC3 B
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid 528 (S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro- 404.11 3.10 LC3 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
529 2,2-Dimethyl-propionic acid (S)-3-{[1-(2- 498.21 3.65 LC3
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-
propionyloxymethyl ester 530
(R)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 398.17 3.32 LC3
pyrazole-3-carbonyl]-amino}-3-phenyl- butyric acid methyl ester 531
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 477.13 2.99 LC8 B
pyrazole-3-carbonyl]-amino}-3-[4-(6-
methoxy-pyridin-3-yl)-phenyl]-propionic acid 532
(S)-3-[(5-Hydroxy-1-o-tolyl-1H-pyrazole-3- 380.14 3.10 LC8 A
carbonyl)-amino]-3-o-tolyl-propionic acid 533
(S)-3-[(1-Benzyl-5-hydroxy-1H-pyrazole-3- 380.14 3.07 LC8 B
carbonyl)-amino]-3-o-tolyl-propionic acid 534
(S)-3-[(5-Methoxy-1-phenyl-1H-pyrazole-3- 380.14 3.29 LC8 A
carbonyl)-amino]-3-o-tolyl-propionic acid 535
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 370.11 2.95 LC8 B
pyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 536
3-(4'-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 460.18 3.14 LC8 A
o-tolyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 537
(S)-3-{[5-Hydroxy-1-(2-trifluoromethyl- 434.11 2.86 LC8 B
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
538 3-[(1-Benzyl-5-hydroxy-1H-pyrazole-3- 460.17 3.12 LC8 B
carbonyl)-amino]-3-(4'-fluoro-biphenyl-4-yl)- propionic acid 539
3-(2'-Chloro-biphenyl-4-yl)-3-[(5-hydroxy-1- 462.11 3.21 LC8 B
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 540
3-(3'-Chloro-biphenyl-4-yl)-3-{[1-(2-chloro- 496.08 3.25 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
541 3-(3'-Chloro-biphenyl-4-yl)-3-{[1-(2-fluoro- 480.11 3.21 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
542 3-(2'-Chloro-biphenyl-4-yl)-3-{[1-(2-fluoro- 480.1 3.14 LC8 A
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
543 3-(4'-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 478.14 3.30 LC8 B
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
544 3-(4'-Fluoro-biphenyl-4-yl)-3-[(5-methoxy-1- 460.15 3.37 LC8 C
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 545
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 458.12 3.20 LC8 C
carbonyl)-amino]-3-(3-methoxy-biphenyl-4- yl)-propionic acid 546
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 450.09 2.95 LC8 B
carbonyl)-amino]-3-(4-methoxy-2- trifluoromethyl-phenyl)-propionic
acid 547 3-(2-Fluoro-5-methoxy-phenyl)-3-[(5- 400.1 2.80 LC8 C
hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 548
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 450.08 3.02 LC8 C
carbonyl)-amino]-3-(2-methoxy-5- trifluoromethyl-phenyl)-propionic
acid 549 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 458.16 3.17 LC8 C
carbonyl)-amino]-3-(4-methoxy-biphenyl-3- yl)-propionic acid 550
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 437.13 2.40 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-
[1,2,4]triazol-1-yl-phenyl)-propionic acid 551
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 476.15 3.12 LC8 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- biphenyl-4-yl)-propionic
acid 552 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 468.09 2.90 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-trifluoromethyl-phenyl)-propionic acid 553
3-(2-Fluoro-5-methoxy-phenyl)-3-{[1-(2- 418.09 2.74 LC8 B
fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic
acid 554 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 468.06 2.94 LC8 C
pyrazole-3-carbonyl]-amino}-3-(2-methoxy-
5-trifluoromethyl-phenyl)-propionic acid 555
3-(2-Fluoro-4-methyl-phenyl)-3-{[1-(2-fluoro- 402.1 2.84 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
556 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 476.14 3.09 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- biphenyl-3-yl)-propionic
acid 557 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 453.12 2.40 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-
[1,2,4]triazol-1-yl-phenyl)-propionic acid 558
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 492.13 3.15 LC8 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- biphenyl-4-yl)-propionic
acid 559 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.07 2.78 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-5-
methoxy-phenyl)-propionic acid 560
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 484.05 2.98 LC8 C
pyrazole-3-carbonyl]-amino}-3-(2-methoxy-
5-trifluoromethyl-phenyl)-propionic acid 561
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.08 2.88 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2-fluoro-4- methyl-phenyl)-propionic
acid 562 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 492.13 3.12 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- biphenyl-3-yl)-propionic
acid 563 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 419.11 2.46 LC8 C
carbonyl)-amino]-3-(4-[1,2,4]triazol-1-yl- phenyl)-propionic acid
564 3-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy- 384.13 2.91 LC8 B
1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 565
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 421.2 2.57 LC8 C
carbonyl)-amino]-3-(4-pyrrolidin-1-yl- phenyl)-propionic acid 566
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 439.18 2.48 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-pyrrolidin- 1-yl-phenyl)-propionic
acid 567 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 484.09 2.93 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-trifluoromethyl-phenyl)-propionic acid 568
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 455.16 2.54 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4-pyrrolidin- 1-yl-phenyl)-propionic
acid 569 3-(4'-Fluoro-biphenyl-4-yl)-3-{[5-hydroxy-1- 514.08 3.16
LC8 B (2-trifluoromethyl-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 570
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 426.14 3.31 LC8
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid isopropyl
ester 571 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 426.15 3.33 LC8
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid propyl ester
572 (S)-3-[(1-Cyclopentyl-5-hydroxy-1H- 358.15 2.89 LC8 B
pyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 573
(S)-3-[(1-Cyclohexyl-5-hydroxy-1H-pyrazole- 372.15 2.99 LC8 A
3-carbonyl)-amino]-3-o-tolyl-propionic acid 574
3-[(1-Cyclopentyl-5-hydroxy-1H-pyrazole-3- 438.14 3.17 LC8 C
carbonyl)-amino]-3-(4'-fluoro-biphenyl-4-yl)- propionic acid 575
3-[(1-Cyclohexyl-5-hydroxy-1H-pyrazole-3- 452.14 3.27 LC8 C
carbonyl)-amino]-3-(4'-fluoro-biphenyl-4-yl)- propionic acid 576
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 514.09 3.28 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4'-
trifluoromethyl-biphenyl-4-yl)-propionic acid 577
(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 440.13 3.47 LC8
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid butyl ester
578 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 416.31 [(M - H).sup.-]
3.65 LC4 C carbonyl)-amino]-3-(4-pyrazol-1-yl-phenyl)- propionic
acid 579 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 496.1 3.35 LC8 C
carbonyl)-amino]-3-(4'-trifluoromethyl- biphenyl-4-yl)-propionic
acid 580 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 452.08 2.69 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-pyrazol-1- yl-phenyl)-propionic
acid 581 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 530.06 3.32 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4'-
trifluoromethyl-biphenyl-4-yl)-propionic acid 582
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 436.1 2.66 LC8 B
pyrazole-3-carbonyl]-amino}-3-(4-pyrazol-1- yl-phenyl)-propionic
acid 583 3-(2'-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 446.09 3.13
LC8 C phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 584
3-(2'-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 464.09 3.06 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
585 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.09 3.09 LC8 B
pyrazole-3-carbonyl]-amino}-3-(2'-fluoro- biphenyl-4-yl)-propionic
acid 586 (S)-3-{[1-(3,5-Difluoro-phenyl)-5-hydroxy- 402.1 3.04 LC8
B 1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 587
3-{[1-(3,5-Difluoro-phenyl)-5-hydroxy-1H- 482.11 3.31 LC8 C
pyrazole-3-carbonyl]-amino}-3-(4'-fluoro-
biphenyl-4-yl)-propionic acid 588
(S)-3-{[1-(2,6-Difluoro-phenyl)-5-hydroxy- 402.08 2.78 LC8 B
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 589
(S)-3-{[1-(3-Chloro-2-fluoro-phenyl)-5- 418.05 2.94 LC8 B
hydroxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid
590 3-{[1-(3-Chloro-2-fluoro-phenyl)-5-hydroxy- 498.06 3.22 LC8 B
1H-pyrazole-3-carbonyl]-amino}-3-(4'-fluoro-
biphenyl-4-yl)-propionic acid 591
3-(2'-Chloro-biphenyl-4-yl)-3-{[1-(2-chloro- 496.07 3.18 LC8 B
phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
592 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-4-methyl- 398.15 2.83 LC8 B
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 593
(S)-3-{[4-Chloro-1-(2-fluoro-phenyl)-5- 432.13 3.17 LC8 B
methoxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid
594 (S)-3-{[4-Bromo-1-(2-fluoro-phenyl)-5- 476.06 3.19 LC8 A
methoxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid
595 (S)-3-{[4-Fluoro-1-(2-fluoro-phenyl)-5- 416.13 2.63 LC5 A
methoxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid
596 (S)-3-(2,3-Dichloro-phenyl)-3-[(5-methoxy-1- 434.03 3.23 LC8 A
phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 597
3-[(5-Methoxy-1-phenyl-1H-pyrazole-3- 443.16 2.46 LC8 B
carbonyl)-amino]-3-(4-pyridin-2-yl-phenyl)- propionic acid 598
3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 461.13 2.42 LC8 A
pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic
acid 599 (S)-3-{[1-(2,5-Difluoro-phenyl)-5-hydroxy- 402.12 2.06 LC7
A 1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 600
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 430.09 1.86 LC7 C
carbonyl)-amino]-3-(4-methanesulfonyl- phenyl)-propionic acid 601
(S)-3-{[5-Hydroxy-1-(3-sulfamoyl-phenyl)- 445.12 1.89 LC7 B
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 602
(S)-3-{[5-Hydroxy-1-(4-sulfamoyl-phenyl)- 445.12 1.88 LC7 C
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 603
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 448.08 1.83 LC7 C
pyrazole-3-carbonyl]-amino}-3-(4- methanesulfonyl-phenyl)-propionic
acid 604 3-{[2-(2-Fluoro-phenyl)-5-methoxy-4-methyl- 412.15 3.16
LC8 2H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 605
3-{[1-(2-Fluoro-phenyl)-5-methoxy-4-methyl- 412.13 1.91 LC7 C
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 606
3-(4'-Fluoro-biphenyl-4-yl)-3-{[5-hydroxy-1- 523.39 [(M - H).sup.-]
3.94 LC4 B (3-sulfamoyl-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-propionic acid 607
(S)-3-{[5-Hydroxy-1-(2-methanesulfonyl- 444.14 1.93 LC7 C
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
608 (S)-3-{[1-(2-Chloro-phenyl)-5-methoxy-1H- 414.12 2.20 LC6 B
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 609
(S)-3-{[1-(3-Fluoro-phenyl)-5-methoxy-1H- 398.15 2.26 LC6 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 610
(S)-3-{[1-(2,5-Difluoro-phenyl)-5-methoxy- 416.15 2.20 LC6 A
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 611
(S)-3-[(1-tert-Butyl-5-methoxy-1H-pyrazole- 360.11 2.25 LC6 B
3-carbonyl)-amino]-3-o-tolyl-propionic acid 612
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 438.17 2.35 LC6 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
613 Pyrrolidine-1-carboxylic acid 5-((S)-2- 481.21 2.25 LC6 A
carboxy-1-o-tolyl-ethylcarbamoyl)-2-(2-
fluoro-phenyl)-2H-pyrazol-3-yl ester 614
(S)-3-{[5-Dimethylcarbamoyloxy-1-(2-fluoro- 455.17 2.15 LC6 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
615 (S)-3-{[5-Dimethylcarbamoylmethoxy-1-(2- 469.15 2.99 LC3 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 616 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-oxo-2- 495.17 3.07 LC3 A
pyrrolidin-1-yl-ethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 617
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-methoxy- 442.25 3.20 LC3 A
ethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
618 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid ethyl ester
619 Piperidine-1-carboxylic acid 5-((S)-2- 495.22 1.70 LC9 A
carboxy-1-o-tolyl-ethylcarbamoyl)-2-(2-
fluoro-phenyl)-2H-pyrazol-3-yl ester 620
(S)-3-{[1-(2-Fluoro-phenyl)-5-(methyl- 517.2 1.71 LC9 A
phenyl-carbamoyloxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 621
(S)-3-[(5-Ethoxy-1-phenyl-1H-pyrazole-3- 394.18 1.69 LC9 A
carbonyl)-amino]-3-o-tolyl-propionic acid 622
(S)-3-[(5-Cyclopropylmethoxy-1-phenyl-1H- 420.19 1.77 LC9 A
pyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 623
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2- 542.22 1.28 LC11 B
trifluoromethyl-benzyloxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 624
(S)-3-{[1-(2-Fluoro-phenyl)-5-(3- 542.31 3.89 LC3 B
trifluoromethyl-benzyloxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 625
(S)-3-{[1-(2-Fluoro-phenyl)-5-phenethyloxy- 488.35 3.70 LC3 A
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 626
(S)-3-{[5-Cyclopentyloxy-1-(2-fluoro-phenyl)- 452.32 3.68 LC3 A
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 627
(S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 482.36 3.34 LC3 A
pyran-4-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 628
(S)-3-{[5-[2-(3,5-Dimethyl-isoxazol-4-yl)- 507.27 1.18 LC11 A
ethoxy]-1-(2-fluoro-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 629
(S)-3-{[1-(2-Fluoro-phenyl)-5-(pyridin-4- 475.33 2.62 LC3 A
ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid
630 (S)-3-{[1-(2-Fluoro-phenyl)-5-isopropoxy-1H- 426.3 3.42 LC3 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 631
(S)-3-{[5-Cyclohexyloxy-1-(2-fluoro-phenyl)- 466.35 3.85 LC3 A
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 632
(S)-3-{[5-(2,2-Dimethyl-propoxy)-1-(2-fluoro- 454.35 3.80 LC3 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
633 (S)-3-{[1-(2-Fluoro-phenyl)-5-isobutoxy-1H- 440.31 3.65 LC3 NO
pyrazole-3-carbonyl]-amino}-3-o-tolyl- DATA propionic acid 634
(S)-3-{[5-Cyclopropylmethoxy-1-(2,6- 456.31 3.54 LC3 A
difluoro-phenyl)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 635
(S)-3-{[5-(2-Cyano-benzyloxy)-1-(2-fluoro- 499.26 3.42 LC3 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
636 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 518.34 1.27 LC11 A
phenyl-propoxy)-1H-pyrazole-3-carbonyl]- amino}-3-p-tolyl-propionic
acid 637 (S)-3-{[5-[2-(2-Ethoxy-ethoxy)-ethoxy]-1-(2- 500.3 3.32
LC3 A fluoro-phenyl)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 638
(S)-3-{[5-Cyclohexylmethoxy-1-(2-fluoro- 480.3 1.33 LC11 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
639 (S)-3-({1-(2-Fluoro-phenyl)-5-[2-(2-oxo- 495.3 2.93 LC3 A
pyrrolidin-1-yl)-ethoxy]-1H-pyrazole-3-
carbonyl}-amino)-3-o-tolyl-propionic acid 640
(S)-3-{[1-(2-Fluoro-phenyl)-5-(pyridin-2- 475.31 2.93 LC3 A
ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid
641 (S)-3-{[1-(2-Fluoro-phenyl)-5-(3-fluoro- 444.26 3.39 LC3 A
propoxy)-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid
642 (S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 468.27 3.24 LC3 A
furan-2-ylmethoxy)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 643
(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl- 479.24 3.30 LC3 A
isoxazol-5-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 644
(S)-3-{[5-(2,6-Difluoro-benzyloxy)-1-(2- 510.26 3.60 LC3 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 645 (S)-3-{[5-(2,2-Difluoro-cyclopropylmethoxy)- 474.12 1.70
LC9 A 1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 646
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-methyl- 495.1 1.60 LC9 A
thiazol-4-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 647
(S)-3-{[1-(2-Fluoro-phenyl)-5-(isoxazol-3- 465.27 3.20 LC3 A
ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid
648 (S)-3-{[5-Cyclobutoxy-1-(2-fluoro-phenyl)- 438.28 3.50 LC3 A
1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 649
(S)-3-{[5-Cyclobutylmethoxy-1-(2-fluoro- 452.29 3.68 LC3 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
650 (S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 468.3 3.18 LC3 A
furan-3-ylmethoxy)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 651
(S)-3-{[5-Benzyloxy-1-(2-fluoro-phenyl)-1H- 474.28 3.65 LC3 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 652
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-5-oxo- 481.29 1.40 LC9 A
pyrrolidin-2-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 653
(S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 482.31 3.47 LC3 A
pyran-2-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 654
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-5-oxo- 481.21 1.42 LC9 A
pyrrolidin-2-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 655
(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methoxy- 504.3 3.65 LC3 A
benzyloxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid
656 (S)-3-{[1-(2-Fluoro-phenyl)-5-(1-methyl-1H- 478.26 1.53 LC9
pyrazol-3-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 657
(S)-3-{[1-(2-Fluoro-phenyl)-5-(5-methyl- 479.25 1.18 LC11 A
isoxazol-3-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 658
(S)-3-{[1-(2-Fluoro-phenyl)-5-(isoxazol-5- 465.25 1.11 LC11 A
ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid
659 (S)-3-{[5-(3,3-Dimethyl-butoxy)-1-(2-fluoro- 468.24 1.90 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
660 (S)-3-{[1-(2-Fluoro-phenyl)-5-hexyloxy-1H- 468.29 1.33 LC11 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 661
1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole- 397.19 3.67 LC12
3-carboxylic acid ((S)-2-carbamoyl-1-o-tolyl- ethyl)-amide 662
(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 412.19 1.60 LC9 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 663
(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl- 468.23 1.57 LC9 A
oxetan-3-ylmethoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 664
3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 416.14 1.57 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
665 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 384.14 1.49 LC9 A
pyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 666
3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 412.17 1.61 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
667 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 414.16 1.54 LC9 B
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
668 (S)-3-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 409.14 1.47 LC9 B
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
669 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 414.16 1.51 LC9 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
670 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 398.16 1.56 LC9 A
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 671
(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 418.11 1.59 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-
amino}-propionic acid 672 3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-
428.18 1.54 LC9 A pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 673
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 452.07 1.65 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
674 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 452.12 1.63 LC9 A
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 675 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 398.16 1.55 LC9
A pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 676
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 418.11 1.55 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
677 3-(4-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 416.16 1.57 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
678 3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)- 402.14 1.52 LC9 B
5-methoxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 679
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 402.14 1.50 LC9 B
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
680 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 452.21 1.18 LC11 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 681 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 452.07 1.63
LC9 A phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 682 3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro- 412.19 1.60 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
683 3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro- 452.07 1.64 LC9 A
phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid
684 3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 456.17 1.70 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(3-fluoro-2-methyl-phenyl)-propionic acid 685
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 424.18 1.63 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3- phenyl-propionic acid 686
3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 452.22 1.73 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2,4-dimethyl-phenyl)-propionic acid 687
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 454.2 1.66 LC9 B
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2-methoxy-phenyl)-propionic acid 688 (S)-3-(4-Cyano-phenyl)-3-{[5-
449.18 1.61 LC9 A cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 689
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 454.19 1.63 LC9 B
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(3-methoxy-phenyl)-propionic acid 690
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 438.2 1.69 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3- m-tolyl-propionic acid
691 (S)-3-(4-Chloro-phenyl)-3-{[5- 458.15 1.71 LC9 B
cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 692
3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 468.22 1.67 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(4-methoxy-2-methyl-phenyl)-propionic acid 693
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.11 1.77 LC9 B
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2,4-dichloro-phenyl)-propionic acid 694
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.16 1.75 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(4-trifluoromethyl-phenyl)-propionic acid 695
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 438.21 1.69 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-p- tolyl-propionic acid
696 (S)-3-(2-Chloro-phenyl)-3-{[5- 458.15 1.68 LC9 A
cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 697
3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 456.2 1.70 LC9
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(4-fluoro-2-methyl-phenyl)-propionic acid 698
3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 442.24 1.21 LC11 B
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(4-fluoro-phenyl)-propionic acid 699
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 442.23 1.21 LC11 B
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2-fluoro-phenyl)-propionic acid 700
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2- 482.18 1.67 LC9 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 701 (S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.16 1.72 LC9
B phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2-trifluoromethyl-phenyl)-propionic acid 702
(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.11 1.74 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2,3-dichloro-phenyl)-propionic acid 703
3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 452.22 1.72 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2,3-dimethyl-phenyl)-propionic acid 704
3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.12 1.76 LC9 A
phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-
(2,5-dichloro-phenyl)-propionic acid 705
3-(2-Chloro-4-methoxy-phenyl)-3-{[5- 488.18 1.70 LC9 A
cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 706
3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 430.18 1.64 LC9 A
pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic
acid 707 (S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 398.18 1.57 LC9 B
pyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 708
3-(2,4-Dimethyl-phenyl)-3-{[5-ethoxy-1-(2- 426.21 1.67 LC9 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 709
(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 428.19 1.60 LC9 B
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
710 (S)-3-(4-Cyano-phenyl)-3-{[5-ethoxy-1-(2- 423.21 1.14 LC11 B
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 711
(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 428.19 1.57 LC9 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
712 (S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 412.22 1.20 LC11 A
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 713
(S)-3-(4-Chloro-phenyl)-3-{[5-ethoxy-1-(2- 432.14 1.21 LC11 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 714
3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 442.23 1.19 LC11 A
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 715
(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 466.18 1.23 LC11 A
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 716 (S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 412.16 1.60 LC9 A
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 717
(S)-3-(2-Chloro-phenyl)-3-{[5-ethoxy-1-(2- 432.14 1.20 LC11 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 718
3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 430.21 1.20 LC11 A
pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic
acid 719 3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 416.19 1.18 LC11 B
pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 720
(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 416.18 1.17 LC11 A
pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 721
(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 466.21 1.21 LC11 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 722 (S)-3-(2,3-Dichloro-phenyl)-3-{[5-ethoxy-1- 466.17 1.23
LC11 A (2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 723 3-(2,3-Dimethyl-phenyl)-3-{[5-ethoxy-1-(2- 426.23 1.22
LC11 A fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic
acid 724 3-(2-Chloro-4-methoxy-phenyl)-3-{[5-ethoxy- 461.64 1.20
LC11 A 1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-
amino}-propionic acid 725 3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H-
446.15 1.22 LC11 A pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2-
methyl-phenyl)-propionic acid 726
(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 413.65 1.19 LC11 B
pyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 727
(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 428.13 1.21 LC11 A
pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 728
3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 442.2 1.24 LC11 A
pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid
729 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 443.66 1.20 LC11 B
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
730 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 439.17 1.16 LC11 B
pyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 731
(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 444.15 1.18 LC11 B
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
732 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 428.25 4.48 LC10 A
pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 733
(S)-3-(4-Chloro-phenyl)-3-{[1-(2-chloro- 448.13 4.55 LC10 A
phenyl)-5-ethoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 734
3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 458.14 1.61 LC9
pyrazole-3-carbonyl]-amino}-3-(4-methoxy-
2-methyl-phenyl)-propionic acid 735
(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 482.08 1.72 LC9 B
pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic
acid 736 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 428.13 1.63 LC9 A
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 737
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro- 448.1 1.64 LC9 A
phenyl)-5-ethoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 738
3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 446.12 1.66 LC9 A
pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic
acid 739 3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 432.11 1.61 LC9 B
pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 740
(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 432.1 1.60 LC9
pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 741
(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 482.08 1.67 LC9 B
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 742 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 482.04 1.71 LC9 A
pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid
743 3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 442.16 1.68 LC9 A
pyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid
744 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-3,3- 484.35 1.23 LC11
A dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 745
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 484.34 10.16 LC13 A
3,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 746
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 484.34 10.35 LC13 A
3,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 747
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 498.3 10.53 LC13 A
2,3,3-trimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 748
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 498.3 10.80 LC13 A
2,3,3-trimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 749
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 442.32 1.16 LC11 A
propoxy)-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid
750 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 470.35 4.19 LC10 A
methyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 751 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 510.25 4.34
LC10 A phenyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 752
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 456.38 3.97 LC10 A
methyl-propoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 753 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.24 1.31
LC11 A phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}-
propionic acid (3) 754 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-
538.24 1.32 LC11 A phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 755
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 456.27 1.19 LC11 A
butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid
756 (S)-3-{[5-(2-Ethyl-2-hydroxy-butoxy)-1-(2- 484.32 1.26 LC11 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 757 (S)-3-{[5-(2-Cyclopropyl-2-hydroxy-propoxy)- 482.31 1.24
LC11 A 1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-
amino}-3-o-tolyl-propionic acid 758
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.28 1.29 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 759
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.3 1.30 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 760
(S)-3-{[5-((R)-2-Cyclopropyl-2-hydroxy- 468.31 1.20 LC11 A
ethoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 761
(S)-3-{[5-((S)-2-Cyclopropyl-2-hydroxy- 468.31 1.21 LC11 A
ethoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 762
(S)-3-(2,4-Dichloro-phenyl)-3-{[5-(2-ethyl-2- 538.17 1.31 LC11 A
hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 763
(S)-3-{[5-((R)-2-Cyclopropyl-2-hydroxy- 482.23 1.24 LC11 A
propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 764
(S)-3-{[5-((S)-2-Cyclopropyl-2-hydroxy- 482.21 1.24 LC11 A
propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid (3) 765
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.36 10.01 LC14 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-o-tolyl-propionic acid 766
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.28 1.26 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-p-tolyl-propionic acid 767
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.3 1.14 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 768
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.35 1.11 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 769
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 530.34 1.25 LC11 A
fluoro-phenyl)-5-((S)-2-hydroxy-2,3-
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 770
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 484.24 1.26 LC11 A
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-o-tolyl-propionic acid 771
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.34 1.27 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 772
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 498.31 1.29 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 773
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)- 490.29 4.68 LC10 A
2-hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 774
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 518.23 1.17 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 775
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.2 1.26 LC11 A
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 776
(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.15 1.3 LC11 A
phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 777
(S)-3-(2-Chloro-phenyl)-3-{[5-(3,3-dimethyl- 502.15 1.28 LC11 A
2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 778
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 509.31 1.25 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 779
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.3 1.28 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 780
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 498.35 1.29 LC11 A
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 781
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 498.32 1.16 LC11 A
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 782
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.23 1.25 LC11 A
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 783
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 500.33 1.25 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(2-methoxy-phenyl)- propionic acid 784
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 538.3 1.27 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(2-trifluoromethyl- phenyl)-propionic acid 785
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.2 1.28 LC11 A
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 786
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)- 476.4 1.16 LC11 A
2-hydroxy-2,3-dimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 787
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 484.25 1.27 LC11 A
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-p-tolyl-propionic acid 788
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.29 1.14 LC11 A
hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-p-tolyl-propionic acid 789
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.3 1.3 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 790
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.28 1.29 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 791
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2- 482.2 1.28 LC11 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-p-tolyl-propionic
acid 792 (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.36 10.46 LC14 A
hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-m-tolyl-propionic acid 793
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.17 1.27 LC11 A
phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 794
(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 504.18 1.28 LC11 A
phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 795
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.31 10.5 LC11 A
phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 796
(S)-3-(3-Chloro-phenyl)-3-{[5-(3,3-dimethyl- 502.17 1.29 LC11 A
2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 797
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.16 1.28 LC11 A
phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 798
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 518.35 1.32 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 799
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 552.32 1.32 LC11 A
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 800 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.15 1.31
LC11 A phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 801
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.28 1.15 LC11 A
hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-p-tolyl-propionic acid 802
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 500.26 1.24 LC11 A
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-(3-methoxy-phenyl)- propionic acid 803
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)- 476.32 1.29 LC11 A
2-hydroxy-2,3-dimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 804
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.36 10.25 LC14 A
hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-m-tolyl-propionic acid 805
(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2- 482.21 1.28 LC11 A
fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-m-tolyl-propionic
acid 806 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 500.35 1.1 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(3-methoxy-phenyl)- propionic acid 807
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 495.25 1.22 LC11 A
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 808
(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 506.22 1.25 LC11 A
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 809
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.31 10.7 LC14 A
phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 810
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 514.24 4.54 LC10 A
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid
811 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 500.26 1.26 LC11 A
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-(2-methoxy-phenyl)- propionic acid 812
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 538.24 1.28 LC11 A
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-(2-trifluoromethyl- phenyl)-propionic acid 813
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-(2- 476.28 1.3 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-propionic acid 814
3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3- 450.25 1.26 LC11 A
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-5-methyl-hexanoic
acid 815 (R)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 504.18 1.29 LC11
A phenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 816
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.2 1.31 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 817
(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 506.28 1.25 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 818
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 498.34 1.3 LC11 A
2,3,3-trimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-4-phenyl-butyric acid 819
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.35 1.29 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 820
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)- 490.36 1.32 LC11 A
2-hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-propionic acid 821
3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 484.37 1.12 LC11 A
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-4-phenyl-butyric acid 822
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 500.34 1.12 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(2-methoxy-phenyl)- propionic acid 823
3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 450.34 1.13 LC11 B
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-5-methyl-hexanoic acid 824
(1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 448.36 1.11 LC11 B
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-cyclopentyl)-acetic acid 825
(1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 448.31 1.25 LC11 B
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-cyclopentyl)-acetic acid 826
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 484.3 1.25 LC11 B
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-4-phenyl-butyric acid 827
3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 470.33 1.1 LC11 B
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-2-phenyl-propionic acid 828
(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 504.18 1.29 LC11 B
phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 829
3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3- 484.24 1.26 LC11 B
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-4-phenyl-butyric
acid 830 3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 470.32 1.23 LC11
B 2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-2-phenyl-propionic acid 832
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 523.33 1.25 LC11 C
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 833
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.29 1.26 LC11 C
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-o-tolyl-propionic acid 834
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 509.31 1.22 LC11 C
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 835
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.27 1.24 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 836
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 509.24 1.23 LC11 C
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-butyric acid 837
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.34 1.25 LC11 C
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-4-phenyl-butyric acid 838
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 484.25 1.26 LC11 C
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-4-phenyl-butyric acid 839
(S)-3-(2,3-Dichloro-phenyl)-3-{[5-(3,3- 536.13 1.31 LC11 A
dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 840
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 500.31 1.23 LC11 C
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(4-methoxy-phenyl)- propionic acid 841
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 450.33 1.26 LC11 C
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-5-methyl-hexanoic acid 842
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 450.25 1.26 LC11
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-5-methyl-hexanoic acid 843
(1-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3- 448.23 1.25 LC11
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-
amino}-cyclopentyl)-acetic acid 844
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.21 1.25 LC11
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 845
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 498.27 1.3 LC11
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 846
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.22 1.25 LC11
phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-
1H-pyrazole-3-carbonyl]-amino}-propionic acid 847
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 530.25 1.25 LC11
fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 848
(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 500.25 1.24 LC11
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-3-(4-methoxy-phenyl)- propionic acid 849
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.2 1.3 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 850
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 500.31 1.1 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(4-methoxy-phenyl)- propionic acid 851
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 464.29 4.56 LC11
2,3,3-trimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-5-methyl-hexanoic acid 852
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 498.27 4.55 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-4-phenyl- butyric acid 853
(1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 462.31 1.29 LC11
2,3,3-trimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-cyclopentyl)-acetic acid 854
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.31 1.27 LC11 B
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 855
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 544.36 1.28 LC11
fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-
trimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid
856 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 514.34 1.27 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
857 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.36 10 LC14 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-o-tolyl-propionic acid 858
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 450.35 1.13 LC11
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-5-methyl-hexanoic acid 859
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 498.37 1.16 LC11 A
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 860
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.34 1.13 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-p-tolyl-propionic acid 861
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.27 1.13 LC11 >30
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 862
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.34 1.11 LC11 B
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 863
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 538.31 1.14 LC11
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(2-trifluoromethyl- phenyl)-propionic acid 864
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.37 1.12 LC11
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-4-phenyl-butyric acid 865
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 495.34 1.08 LC11
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 866
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 530.34 1.12 LC11
fluoro-phenyl)-5-((R)-2-hydroxy-2,3-
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 867
(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 509.36 1.09 LC11
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 868
(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 506.32 1.12 LC11
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 869
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.33 1.11 LC11
phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 870
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.38 1.13 LC11 A
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-o-tolyl-propionic acid 871
3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 450.35 1.13 LC11
2,3-dimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-5-methyl-hexanoic acid 872
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.33 1.24 LC11 B
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 873
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.31 1.26 LC11
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 874
(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 495.28 1.22 LC11
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 875
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 500.31 1.24 LC11
hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-
3-carbonyl]-amino}-3-(3-methoxy-phenyl)- propionic acid 876
(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.3 1.25 LC11
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 877
(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.24 1.27 LC11 B
phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 878
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 464.34 1.29 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-5-methyl- hexanoic acid 879
(1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 462.31 1.29 LC11
2,3,3-trimethyl-butoxy)-1H-pyrazole-3-
carbonyl]-amino}-cyclopentyl)-acetic acid 880
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.31 1.29 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 881
(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 512.37 1.32 LC11
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 883
(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.3 1.29 LC11 A
phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 884
(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 544.35 1.29 LC11 A
fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-
trimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid
885 (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 514.24 4.54 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid
886 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 464.36 1.31 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-5-methyl- hexanoic acid 888
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 552.32 1.3 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic
acid 889 (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 523.33 1.26 LC11
phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 890
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 514.36 1.26 LC11
hydroxy-2,3,3-trimethyl-butoxy)-1H-
pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid
891 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 518.26 4.46 LC10 A
phenyl-propoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic
acid 892 1-(2-Fluoro-phenyl)-5-methoxy-1H- 488.38 1 LC11
pyrazole-3-carboxylic acid {(S)-2-[(pyridin-
2-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}- amide; compound with
trifluoro-acetic acid 893 1-(2-Fluoro-phenyl)-5-methoxy-1H- 451.37
1.13 LC11
pyrazole-3-carboxylic acid [(S)-2-
(cyclopropylmethyl-carbamoyl)-1-o-tolyl- ethyl]-amide 894
1-(2-Fluoro-phenyl)-5-methoxy-1H- 477.36 1.12 LC11
pyrazole-3-carboxylic acid {(S)-2-[(furan-2-
ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide 895
1-(2-Fluoro-phenyl)-5-methoxy-1H- 482.44 0.91 LC11
pyrazole-3-carboxylic acid [(S)-2-(3-
dimethylamino-propylcarbamoyl)-1-o-tolyl- ethyl]-amide; compound
with trifluoro- acetic acid 896 1-(2-Fluoro-phenyl)-5-methoxy-1H-
467.44 1.17 LC11 pyrazole-3-carboxylic acid [(S)-2-(1-ethyl-
propylcarbamoyl)-1-o-tolyl-ethyl]-amide 897
1-(2-Fluoro-phenyl)-5-methoxy-1H- 479.05 1.18 LC11
pyrazole-3-carboxylic acid ((S)-2-
cyclohexylcarbamoyl-1-o-tolyl-ethyl)-amide 898
1-(2-Fluoro-phenyl)-5-methoxy-1H- 467.41 1.04 LC11
pyrazole-3-carboxylic acid [(S)-3-((S)-3-
hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl- propyl]-amide 899
1-(2-Fluoro-phenyl)-5-methoxy-1H- 481.4 4.71 LC10
pyrazole-3-carboxylic acid [(S)-1-o-tolyl-2-
((R)-1,2,2-trimethyl-propylcarbamoyl)- ethyl]-amide 900
1-(2-Fluoro-phenyl)-5-methoxy-1H- 467.36 1.04 LC11
pyrazole-3-carboxylic acid [(S)-3-((R)-3-
hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl- propyl]-amide 901
1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.15 LC11
pyrazole-3-carboxylic acid [(S)-2-((S)-sec-
butylcarbamoyl)-1-o-tolyl-ethyl]-amide 902
1-(2-Fluoro-phenyl)-5-methoxy-1H- 481.25 1.07 LC11
pyrazole-3-carboxylic acid [(S)-3-((S)-3-
hydroxy-piperidin-1-yl)-3-oxo-1-o-tolyl- propyl]-amide 903
1-(2-Fluoro-phenyl)-5-methoxy-1H- 468.23 1.02 LC11
pyrazole-3-carboxylic acid [(S)-2-
(carbamoylmethyl-methyl-carbamoyl)-1-o- tolyl-ethyl]-amide 904
1-(2-Fluoro-phenyl)-5-methoxy-1H- 465.25 1.16 LC11
pyrazole-3-carboxylic acid [(S)-2-((R)-1-
cyclopropyl-ethylcarbamoyl)-1-o-tolyl- ethyl]-amide 905
1-(2-Fluoro-phenyl)-5-methoxy-1H- 465.25 1.16 LC11
pyrazole-3-carboxylic acid [(S)-2-((S)-1-
cyclopropyl-ethylcarbamoyl)-1-o-tolyl- ethyl]-amide 906
1-(2-Fluoro-phenyl)-5-methoxy-1H- 451.39 1.13 LC11
pyrazole-3-carboxylic acid ((S)-2-
cyclobutylcarbamoyl-1-o-tolyl-ethyl)-amide 907
1-(2-Fluoro-phenyl)-5-methoxy-1H- 488.42 0.95 LC11
pyrazole-3-carboxylic acid {(S)-2-[(pyridin-
3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}- amide; compound with
trifluoro-acetic acid 908 1-(2-Fluoro-phenyl)-5-methoxy-1H- 465.43
1.16 LC11 pyrazole-3-carboxylic acid ((S)-2-
cyclopentylcarbamoyl-1-o-tolyl-ethyl)- amide 909
1-(2-Fluoro-phenyl)-5-methoxy-1H- 469.4 1.11 LC11
pyrazole-3-carboxylic acid [(S)-2-(2-
methoxy-1-methyl-ethylcarbamoyl)-1-o- tolyl-ethyl]-amide 910
1-(2-Fluoro-phenyl)-5-methoxy-1H- 461.2 1.11 LC11
pyrazole-3-carboxylic acid [(S)-2-(2,2-
difluoro-ethylcarbamoyl)-1-o-tolyl-ethyl]- amide 911
1-(2-Fluoro-phenyl)-5-methoxy-1H- 479.18 1.14 LC11
pyrazole-3-carboxylic acid [(S)-1-o-tolyl-2-
(2,2,2-trifluoro-ethylcarbamoyl)-ethyl]- amide 912
1-(2-Fluoro-phenyl)-5-methoxy-1H- 465.25 1.16 LC11
pyrazole-3-carboxylic acid [(S)-2-(2-
cyclopropyl-ethylcarbamoyl)-1-o-tolyl- ethyl]-amide 913
1-(2-Fluoro-phenyl)-5-methoxy-1H- 489.23 1.02 LC11
pyrazole-3-carboxylic acid {(S)-2-
[(pyrimidin-5-ylmethyl)-carbamoyl]-1-o- tolyl-ethyl}-amide 914
1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.15 LC11
pyrazole-3-carboxylic acid ((S)-2-
butylcarbamoyl-1-o-tolyl-ethyl)-amide 915
1-(2-Fluoro-phenyl)-5-methoxy-1H- 477.22 1.12 LC11
pyrazole-3-carboxylic acid {(S)-2-[(furan-3-
ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide 916
1-(2-Fluoro-phenyl)-5-methoxy-1H- 488.41 0.92 LC11 C
pyrazole-3-carboxylic acid {(S)-2-[(pyridin-
4-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}- amide; compound with
trifluoro-acetic acid 917 1-(2-Fluoro-phenyl)-5-methoxy-1H- 467.44
1.19 LC11 C pyrazole-3-carboxylic acid [(S)-2-(1,1-
dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]- amide 918
1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.15 LC11 C
pyrazole-3-carboxylic acid [(S)-2-((R)-sec-
butylcarbamoyl)-1-o-tolyl-ethyl]-amide 919
1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.37 1.15 LC11 C
pyrazole-3-carboxylic acid ((S)-2-
isobutylcarbamoyl-1-o-tolyl-ethyl)-amide 920
1-(2-Fluoro-phenyl)-5-methoxy-1H- 481.51 1.2 LC11 C
pyrazole-3-carboxylic acid [(S)-1-o-tolyl-2-
((S)-1,2,2-trimethyl-propylcarbamoyl)- ethyl]-amide 921
1-(2-Fluoro-phenyl)-5-methoxy-1H- 483.26 1.13 LC11 C
pyrazole-3-carboxylic acid [(S)-2-(1-
methoxymethyl-propylcarbamoyl)-1-o-tolyl- ethyl]-amide 922
1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.17 LC11 C
pyrazole-3-carboxylic acid ((S)-2-tert-
butylcarbamoyl-1-o-tolyl-ethyl)-amide 923
1-(2-Fluoro-phenyl)-5-methoxy-1H- 477.23 1.07 LC11 C
pyrazole-3-carboxylic acid [(S)-2-(5-
methyl-1H-pyrazol-3-ylcarbamoyl)-1-o- tolyl-ethyl]-amide 924
1-(2-Fluoro-phenyl)-5-methoxy-1H- 467.38 1.08 LC11 A
pyrazole-3-carboxylic acid [(S)-2-(2,2-
dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]- amide 925
1-(2-Fluoro-phenyl)-5-methoxy-1H- 483.41 1.09 LC11 C
pyrazole-3-carboxylic acid [(S)-2-(3-
hydroxy-2,2-dimethyl-propylcarbamoyl)-1- o-tolyl-ethyl]-amide 926
1-(2-Fluoro-phenyl)-5-methoxy-1H- 436.2 1.07 LC11 C
pyrazole-3-carboxylic acid [(S)-2-
(cyanomethyl-carbamoyl)-1-o-tolyl-ethyl]- amide 927
1-(2-Fluoro-phenyl)-5-methoxy-1H- 483.26 1.09 LC11 B
pyrazole-3-carboxylic acid [(S)-2-((R)-1-
hydroxymethyl-2-methyl-propylcarbamoyl)- 1-o-tolyl-ethyl]-amide 928
1-(2-Fluoro-phenyl)-5-methoxy-1H- 479.22 1.02 LC11 B
pyrazole-3-carboxylic acid {(S)-2-[(1H-
tetrazol-5-ylmethyl)-carbamoyl]-1-o-tolyl- ethyl}-amide 929
1-(2-Fluoro-phenyl)-5-methoxy-1H- 439.39 1.12 LC11 B
pyrazole-3-carboxylic acid ((S)-2-
isopropylcarbamoyl-1-o-tolyl-ethyl)-amide 930
1-(2-Fluoro-phenyl)-5-methoxy-1H- 477.23 1.08 LC11 B
pyrazole-3-carboxylic acid [(S)-2-(1-
methyl-1H-pyrazol-3-ylcarbamoyl)-1-o- tolyl-ethyl]-amide 931
1-(2-Fluoro-phenyl)-5-methoxy-1H- 480.24 1.01 LC11 C
pyrazole-3-carboxylic acid [(S)-2-(2-oxo-
pyrrolidin-3-ylcarbamoyl)-1-o-tolyl-ethyl]- amide 932
1-(2-Fluoro-phenyl)-5-methoxy-1H- 478.36 1.13 LC11 B
pyrazole-3-carboxylic acid [(S)-2-(5-
methyl-isoxazol-3-ylcarbamoyl)-1-o-tolyl- ethyl]-amide 933
1-(2-Fluoro-phenyl)-5-methoxy-1H- 437.29 1.08 LC11 A
pyrazole-3-carboxylic acid ((S)-2-
cyclopropylcarbamoyl-1-o-tolyl-ethyl)- amide 934
1-(2-Fluoro-phenyl)-5-methoxy-1H- 478.22 1.08 LC11 A
pyrazole-3-carboxylic acid {(S)-2-
[(isoxazol-5-ylmethyl)-carbamoyl]-1-o-tolyl- ethyl}-amide 935
1-(2-Fluoro-phenyl)-5-methoxy-1H- 455.37 1.08 LC11 A
pyrazole-3-carboxylic acid [(S)-2-(2-
methoxy-ethylcarbamoyl)-1-o-tolyl-ethyl]- amide 936
1-(2-Fluoro-phenyl)-5-methoxy-1H- 483.43 1.09 LC11 A
pyrazole-3-carboxylic acid [(S)-2-((S)-1-
hydroxymethyl-2-methyl-propylcarbamoyl)- 1-o-tolyl-ethyl]-amide 937
1-(2-Fluoro-phenyl)-5-methoxy-1H- 469.24 1.1 LC11 A
pyrazole-3-carboxylic acid [(S)-2-((S)-2-
methoxy-1-methyl-ethylcarbamoyl)-1-o- tolyl-ethyl]-amide 938
1-(2-Fluoro-phenyl)-5-methoxy-1H- 481.25 1.1 LC11 A
pyrazole-3-carboxylic acid ((S)-2-{[(S)-1-
(tetrahydro-furan-2-yl)methyl]-carbamoyl}- 1-o-tolyl-ethyl)-amide
939 1-(2-Fluoro-phenyl)-5-methoxy-1H- 467.23 1.09 LC11 A
pyrazole-3-carboxylic acid [(S)-2-((R)-1,2-
dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]- amide (1) Mass
spectroscopic chracterization; observed mass number of the ion [(M
+ H).sup.+], unless specified otherwise (2) Cathepsin A inhibitory
activity determined in the pharmacological test "Cathepsin A
inhibitory activity" described blow. "A" means an IC.sub.50 value
of less than 0.1 .mu.M, "B" ,eams am IC.sub.50 value between 0.1
.mu.M and 1 .mu.M, "C" means an IC.sub.50 value between 1 .mu.M and
30 .mu.M. (3) The two compounds of examples 745 and 746; the two
compounds of examples 747 and 748; the two compounds of examples
753 and 754; the two compounds of examples 758 and 759; the two
compounds of examples 760 and 761; and the two compounds of
examples 763 and 764 each are two diastereomeric compounds, one of
them being the disatereomer with R configuration in the alcohol
moeity and the other of them being the diastereomer with S
configuration in the alcohol moiety (the stereochemistry in the
alcohol moiety was not determined; it was arbitrarily assigned R
configuration in the first diastereomer eluted from the
chromatography column and S configuration in the second
diastereomer eluted from the chromatography column).
Exemplary .sup.1H-NMR Data of Example Compounds
EXAMPLE 3
[0623] .delta. (ppm)=2.75 (dd, 1H); 2.92 (dd, 1H); 3.75 (s, 3H);
5.35 (q, 1H); 5.85 (s, 1H); 6.85 (d, 2H); 7.3 (m, 3H); 7.5 (m, 2H);
7.75 (d, 2H); 8.5 (d, 1H)
EXAMPLE 7
[0624] .delta. (ppm)=1.25 (s, 9H); 2.0 (s, 3H); 2.3 (s, 3H); 2.75
(dd, 1H); 2.9 (dd, 1H); 5.35 (q, 1H); 5.8 (s, 1H); 6.7 (m, 1H);
7.05-7.3 (m, 6H); 8.5 (d, 1H)
EXAMPLE 129
[0625] .delta. (ppm)=2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 3.9
(s, 3H); 5.6 (q, 1H); 6.2 (s, 1H); 7.1 (m, 3H); 7.4 (m, 1H); 7.5
(m, 2H); 7.6 (m, 2H); 8.65 (d, 1H)
EXAMPLE 523
[0626] .delta. (ppm)=2.35 (s, 3H); 2.75 (dd, 1H); 2.9 (dd, 1H); 5.6
(q, 1H); 5.85 (s, 1H); 7.0 (t, 1H); 7.2 (q, 1H); 7.35 (m, 3H); 7.8
(m, 2H); 8.65 (d, 1H)
EXAMPLE 524
[0627] .delta. (ppm)=2.7 (dd, 1H); 2.9 (dd, 1H); 5.7 (m, 1H); 5.85
(s, 1H); 7.25 (m, 1H); 7.3-7.4 (m, 3H); 7.45 (m, 1H); 7.8 (m, 2H);
8.75 (d, 2H)
EXAMPLE 534
[0628] .delta. (ppm)=2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 5.6
(s, 1H); 6.25 (s, 1H); 7.1 (m, 3H); 7.35 (m, 1H); 7.5 (m, 3H); 7.7
(d, 2H); 8.65 (d, 1H)
EXAMPLE 548
[0629] .delta. (ppm)=2.7 (dd, 1H); 2.85 (dd, 1H); 3.9 (s, 3H); 5.7
(m, 1H); 5.9 (s, 1H); 7.2 (d, 1H); 7.35 (t, 1H); 7.5 (t, 2H); 7.6
(d, 1H); 7.65 (s, 1H); 7.8 (d, 2H); 8.6 (d, 1H)
EXAMPLE 564
[0630] .delta. (ppm)=2.3 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 5.6
(m, 1H); 5.85 (s, 1H); 7.0 (m, 2H); 7.35 (m, 2H); 7.5 (m, 2H); 7.8
(m, 2H); 8.6 (d, 1H)
EXAMPLE 585
[0631] .delta. (ppm)=2.85 (dd, 1H); 3.0 (dd, 1H); 5.4 (q, 1H); 5.8
(s, 1H); 7.2-7.6 (m, 12H); 8.6 (d, 1H)
EXAMPLE 597
[0632] .delta. (ppm)=2.85 (dd, 1H); 3.0 (dd, 1H); 3.95 (s, 3H); 5.5
(q, 1H); 6.25 (s, 1H); 7.3-8.6 (several m, 13H); 8.75 (d, 1H)
EXAMPLE 603
[0633] .delta. (ppm)=2.8 (dd, 1H); 3.0 (dd, 1H); 3.2 (s, 3H); 5.45
(q, 1H); 5.8 (s, 1H); 7.3 (t, 1H); 7.4 (t, 1H); 7.55 (m, 2H); 7.6
(d, 2H); 7.85 (d, 2H); 8.75 (d, 1H)
EXAMPLE 607
[0634] .delta. (ppm)=2.4 (s, 3H); 2.6 (dd, 1H); 2.8 (dd, 1H); 5.6
(m, H); 5.8 (s, 1H); 7.1 (m, 3H); 7.4 (m, 1H); 7.6 (d, 1H); 7.8 (m,
1H); 7.9 (m, 1H); 8.1 (m, 1H); 8.6 (d, 1H)
EXAMPLE 618
[0635] .delta. (ppm)=1.05 (t, 3H); 2.4 (s, 3H); 2.8 (dd, 1H); 2.95
(dd, 1H); 3.9 (s, 3H); 4.0 (q, 2H); 5.5 (q, 1H); 6.2 (s, 1H); 7.1
(m, 3H); 7.35 (m, 1H); 7.45 (m, 2H); 7.55 (m, 2H); 8.7 (d, 1H)
EXAMPLE 672
[0636] .delta. (ppm)=2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 3.7
(s, 3H); 3.9 (s, 3H); 5.6 (q, 1H); 6.2 (s, 1H); 6.7 (m, 2H); 7.35
(m, 2H); 7.45 (m, 1H); 7.55 (m, 2H); 8.55 (d, 1H)
EXAMPLE 680
[0637] .delta. (ppm)=3.0 (m, 2H); 3.9 (s, 3H); 5.8 (m, 1H); 6.2 (s,
1H); 7.45 (m, 1H); 7.55 (m, 2H); 7.5-7.7 (m, 4H); 7.8 (m, 1H); 8.9
(d, 1H)
EXAMPLE 682
[0638] .delta. (ppm)=2.2 (s, 3H); 2.3 (s, 3H); 2.65 (dd, 1H); 2.9
(dd, 1H); 3.9 (s, 3H); 5.7 (q, 1H); 6.2 (s, 1H); 7.0 (m, 2H); 7.3
(m, 1H); 7.35 (m, 1H); 7.45 (m, 1H); 7.55 (m, 2H); 8.6 (d, 1H)
EXAMPLE 684
[0639] .delta. (ppm)=0.3 (m, 2H); 0.5 (m, 2H); 1.2 (m, 1H); 2.3 (s,
3H); 2.75 (dd, 1H); 2.9 (dd, 1H); 4.0 (d, 2H); 5.6 (q, 1H); 6.2 (s,
1H); 7.0 (m, 1H); 7.2 (m, 1H); 7.3 (m, 1H); 7.35 (m, 1H); 7.45 (m,
1H); 7.55 (m, 2H); 8.75 (d, 1H)
EXAMPLE 690
[0640] .delta. (ppm)=0.3 (m, 2H); 0.5 (m, 2H); 1.2 (m, 1H); 2.25
(s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 4.0 (d, 2H); 5.3 (q, 1H); 6.2
(s, 1H); 7.0 (m, 1H); 7.2 (m, 2H); 7.35 (m, 1H); 7.45 (m, 1H); 7.55
(m, 2H); 8.6 (d, 2H)
EXAMPLE 700
[0641] .delta. (ppm)=1.1 (s, 9H); 2.4 (s, 3H); 2.7 (dd, 1H); 2.9
(dd, 1H); 5.25 (s, 2H); 5.6 (q, 1H); 6.1 (s, 1H); 7.1 (m, 3H); 7.35
(m, 1H); 7.45 (m, 2H); 7.55-7.7 (m, 2H); 8.7 (d, 1H)
EXAMPLE 744
[0642] .delta. (ppm)=0.8 (s, 9H); 2.45 (s, 3H); 2.7 (m, 1H); 2.9
(m, 1H); 3.9 (m, 1H); 4.2 (m, 1H); 4.9 (m, 1H); 5.6 (q, 1H); 6.2
(s, 1H); 7.1 (m, 3H); 7.35 (m, 1H); 7.45 (m, 2H); 7.55 (m, 2H);
8.65 (d, 1H)
EXAMPLE 751
[0643] .delta. (ppm)=1.05 (s, 6H); 2.65 (dd, 1H); 2.9 (dd, 1H); 3.9
(s, 2H); 5.7 (m, 1H); 6.2 (s, 1H); 7.3-7.6 (m, 7H); 8.8 (d, 1H)
EXAMPLE 757
[0644] .delta. (ppm)=0.1-0.25 (m, 3H); 0.3 (m, 1H); 0.7 (m, 1H);
1.05 (s, 3H); 2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (m, 1H); 3.9 (m, 2H);
5.6 (m, 1H); 6.2 (s, 1H); 7.1 (m, 3H); 7.35 (m, 1H); 7.45 (m, 2H);
7.6 (m, 2H); 8.6 (d, 1H)
EXAMPLE 758
[0645] .delta. (ppm)=0.8 (s, 9H); 1.05 (s, 3H); 2.65 (dd, 1H); 2.9
(dd, 1H); 3.95 (d, 1H); 4.1 (d, 1H); 5.75 (m, 1H); 6.2 (s, 1H);
7.3-7.6 (m, 8H); 8.8 (d, 1H)
EXAMPLE 759
[0646] .delta. (ppm)=0.8 (s, 9H); 1.0 (s, 3H); 2.65 (dd, 1H); 2.9
(m, 1H); 4.0 (d, 1H); 4.1 (d, 1H); 5.75 (m, 1H); 6.25 (s, 1H);
7.25-7.6 (m, 8H); 8.8 (d, 1H)
EXAMPLE 762
[0647] .delta. (ppm)=0.7 (t, 6H); 1.3 (m, 4H); 2.65 (dd, 1H); 2.9
(dd, 1H); 3.9 (s, 2H); 5.7 (m, 1H); 6.2 (s, 1H); 7.3-7.6 (m, 7H);
8.85 (d, 1H)
Pharmacological Tests
a) Cathepsin a Inhibitory Activity
[0648] Recombinant human cathepsin A (residues 29-480, with a
C-terminal 10-His tag; R&D Systems, #1049-SE) was
proteolytically activated with recombinant human cathepsin L
(R&D Systems, #952-CY). Briefly, cathepsin A was incubated at
10 .mu.g/ml with cathepsin L at 1 .mu.g/ml in activation buffer (25
mM 2-(morpholin-4-yl)-ethanesulfonic acid (MES), pH 6.0, containing
5 mM dithiothreitol (DTT)) for 15 min at 37.degree. C. Cathepsin L
activity was then stopped by the addition of the cysteine protease
inhibitor E-64
(N-(trans-epoxysuccinyl)-L-leucine-4-guanidinobutylamide;
Sigma-Aldrich, #E3132; dissolved in activation buffer/DMSO) to a
final concentration of 10 .mu.M.
[0649] The activated cathepsin A was diluted in assay buffer (25 mM
MES, pH 5.5, containing 5 mM DTT) and mixed with the test compound
(dissolved in assay buffer containing (v/v) 3% DMSO) or, in the
control experiments, with the vehicle in a multiple assay plate.
After incubation for 15 min at room temperature, as substrate then
bradykinin carrying an N-terminal.RTM.Bodipy FL
(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl)
label (JPT Peptide Technologies GmbH; dissolved in assay buffer)
was added to the mixture. The final concentration of cathepsin A
was 833 ng/ml and the final concentration of labeled bradykinin 2
.mu.M. After incubation for 15 min at room temperature the reaction
was stopped by the addition of stop buffer (130 mM
2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4,
containing (v/v) 0.013% Triton X-100, 0.13% Coating Reagent 3
(Caliper Life Sciences), 6.5% DMSO and 20 .mu.M ebelactone B
(Sigma, #E0886)).
[0650] Uncleaved substrate and product were then separated by a
microfluidic capillary electrophoresis on a LabChip.RTM. 3000 Drug
Discovery System (12-Sipper-Chip; Caliper Life Sciences) and
quantified by determination of the respective peak areas. Substrate
turnover was calculated by dividing product peak area by the sum of
substrate and product peak areas, and the enzyme activity and the
inhibitory effect of the test compound thus quantified. From the
percentage of inhibition of cathepsin A activity observed with the
test compound at several concentrations, the inhibitory
concentration IC.sub.50, i.e. the concentration which effects 50%
inhibition of enzyme activity was, calculated. IC.sub.50 values of
various example compounds are given in Table 1, wherein "A" means
an IC.sub.50 value of less than 0.1 .mu.M, "B" means an IC.sub.50
value between 0.1 .mu.M and 1 .mu.M, and "C" means an IC.sub.50
value between 1 .mu.M and 30 .mu.M.
B) In Vivo Antihypertrophic and Renoprotective Activity
[0651] The in vivo pharmacological activity of the compounds of the
invention can be investigated, for example, in the model of
DOCA-salt sensitive rats with unilateral nephrectomy. Briefly, in
this model unilateral nephrectomy of the left kidney (UNX) is
performed on Sprague Dawley rats of 150 g to 200 g of body weight.
After the operation as well as at the beginning of each of the
following weeks 30 mg/kg of body weight of DOCA
(desoxycorticosterone acetate) are administered to the rats by
subcutaneous injection. The nephrectomized rats treated with DOCA
are supplied with drinking water containing 1% of sodium chloride
(UNX/DOCA rats). The UNX/DOCA rats develop high blood pressure,
endothelial dysfunction, myocardial hypertrophy and fibrosis as
well as renal dysfunction. In the test group (UNX/DOCA Test) and
the placebo group (UNX/DOCA Placebo), which consist of randomized
UNX/DOCA rats, the rats are treated orally by gavage in two part
administrations at 6 a.m. and 6 p.m. with the daily dose of the
test compound (for example 10 mg/kg of body weight dissolved in
vehicle) or with vehicle only, respectively. In a control group
(control), which consists of animals which have not been subjected
to UNX and DOCA administration, the animals receive normal drinking
water and are treated with vehicle only. After five weeks of
treatment, systolic blood pressure (SBP) and heart rate (HR) are
measured non-invasively via the tail cuff method. For determination
of albuminuria and creatinine, 24 h urine is collected on metabolic
cages. Endothelial function is assessed in excised rings of the
thoracic aorta as described previously (W. Linz et al., JRAAS
(Journal of the renin-angiotensin-aldosterone system) 7 (2006),
155-161). As a measure of myocardial hypertrophy and fibrosis,
heart weight, left ventricular weight and the relation of
hydroxyproline and proline are determined in excised hearts.
TABLE-US-00002 TABLE 2 Cathepsin A inhibitory activity IC.sub.50
CATH-A Example Compound Name IC.sub.50 (.mu.M) 129
(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-
0.041249 amino}-3-o-tolyl-propionic acid 135
(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.210567 amino}-3-p-tolyl-propionic acid 221
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.322137
amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 385
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.060742 amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic
acid 418 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
5.287222 amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic
acid 441 3-(2-Fluoro-6-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H-
0.513333 pyrazole-3-carbonyl)-amino]-propionic acid 443
3-(5-Fluoro-2-trifluoromethyl-phenyl)-3-[(5-hydroxy-1-phenyl-
0.220464 1H-pyrazole-3-carbonyl)-amino]-propionic acid 444
3-(2,5-Dichloro-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3-
0.083052 carbonyl)-amino]-propionic acid 445
(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-
0.129975 p-tolyl-propionic acid 446
(S)-3-(2-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3-
0.120455 carbonyl)-amino]-propionic acid 447
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.114465 amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 448
3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1-(2,4-difluoro-phenyl)-
0.883729 5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid
449 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.175869 amino}-3-(2-fluoro-6-methoxy-phenyl)-propionic acid 450
3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1-(2,4-difluoro-phenyl)-
0.408735 5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid
451
3-(2,5-Difluoro-phenyl)-3-{[1-(2,4-difluoro-phenyl)-5-hydroxy-1H-
0.232875 pyrazole-3-carbonyl]-amino}-propionic acid 452
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.138677 amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic
acid 453
3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.248853 amino}-3-(5-fluoro-2-methoxy-phenyl)-propionic acid 454
(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3- 0.185593
carbonyl]-amino}-3-p-tolyl-propionic acid 455
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.154288
amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 457
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.170335
amino}-3-(2-fluoro-6-methoxy-phenyl)-propionic acid 458
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-chloro-phenyl)-5-hydroxy-
0.2227 1H-pyrazole-3-carbonyl]-amino}-propionic acid 459
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.128099
amino}-3-(2,5-difluoro-phenyl)-propionic acid 460
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.117776
amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 461
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.150702
amino}-3-(5-fluoro-2-methyl-phenyl)-propionic acid 462
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.080429
amino}-3-(2,5-dichloro-phenyl)-propionic acid 463
3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1-(3-chloro-phenyl)-5-
11.052896 hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 464
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.27418
amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 465
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.738351
amino}-3-(2,5-difluoro-phenyl)-propionic acid 466
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.561884
amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 467
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 2.24854
amino}-3-(2-trifluoromethylsulfanyl-phenyl)-propionic acid 468
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.279829
amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 469
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.860051
amino}-3-(2-fluoro-6-methoxy-phenyl)-propionic acid 470
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-chloro-phenyl)-5-hydroxy-
0.398363 1H-pyrazole-3-carbonyl]-amino}-propionic acid 471
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.486287
amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 472
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 4.087942
amino}-3-(2,5-difluoro-phenyl)-propionic acid 473
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 1.726107
amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 474
(S)-3-(2-Chloro-phenyl)-3-{[1-(4-chloro-phenyl)-5-hydroxy-1H-
0.206959 pyrazole-3-carbonyl]-amino}-propionic acid 475
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-hydroxy-
0.136696 1H-pyrazole-3-carbonyl]-amino}-propionic acid 492
3-(5-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-
0.175259 1H-pyrazole-3-carbonyl]-amino}-propionic acid 493
3-(2,5-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-
0.245667 pyrazole-3-carbonyl]-amino}-propionic acid 494
3-(3-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.142178
pyrazole-3-carbonyl)-amino]-propionic acid 495
3-(2-Chloro-5-fluoro-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.213013
pyrazole-3-carbonyl)-amino]-propionic acid 496
3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-[(5-hydroxy-1-phenyl-
0.166522 1H-pyrazole-3-carbonyl)-amino]-propionic acid 497
3-(5-Fluoro-2-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.145434
pyrazole-3-carbonyl)-amino]-propionic acid 498
3-(5-Fluoro-2-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.142545
pyrazole-3-carbonyl)-amino]-propionic acid 499
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-
0.147004 pyridin-2-yl-phenyl)-propionic acid; compound with
trifluoro- acetic acid 500
3-(2,5-Dichloro-phenyl)-3-{[1-(2,4-difluoro-phenyl)-5-hydroxy-
0.086296 1H-pyrazole-3-carbonyl]-amino}-propionic acid 502
(S)-3-(2-Chloro-phenyl)-3-{[1-(2,4-difluoro-phenyl)-5-hydroxy-
0.116138 1H-pyrazole-3-carbonyl]-amino}-propionic acid 503
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.391391
amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 504
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.123363
amino}-3-(5-fluoro-2-methoxy-phenyl)-propionic acid 505
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
29.754902 amino}-3-(4-morpholin-4-yl-phenyl)-propionic acid 506
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.05236
amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 507
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-hydroxy-1H-
0.160998 pyrazole-3-carbonyl]-amino}-propionic acid 508
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.136863
amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 509
3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(3-chloro-phenyl)-5-hydroxy-
0.100369 1H-pyrazole-3-carbonyl]-amino}-propionic acid 510
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.175019
amino}-3-(5-fluoro-2-methyl-phenyl)-propionic acid 511
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.101707
amino}-3-(2,5-dichloro-phenyl)-propionic acid 512
(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.155051 amino}-3-p-tolyl-propionic acid 513
3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.194548
amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 514
(S)-3-(2-Chloro-phenyl)-3-{[1-(3-chloro-phenyl)-5-hydroxy-1H-
0.303517 pyrazole-3-carbonyl]-amino}-propionic acid 515
3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.238394
amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 516
3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-hydroxy-
0.10191 1H-pyrazole-3-carbonyl]-amino}-propionic acid 525
3-(5-Fluoro-2-methoxy-phenyl)-3-{[1-(4-fluoro-phenyl)-5- 1.505027
hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 526
(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-
0.357948 amino}-3-p-tolyl-propionic acid 527
3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.152264
amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 528
(S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-
0.413048 pyrazole-3-carbonyl]-amino}-propionic acid 545
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(3-
1.112898 methoxy-biphenyl-4-yl)-propionic acid 546
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-
0.532645 methoxy-2-trifluoromethyl-phenyl)-propionic acid 547
3-(2-Fluoro-5-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 1.388069
pyrazole-3-carbonyl)-amino]-propionic acid 548
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(2-
7.759644 methoxy-5-trifluoromethyl-phenyl)-propionic acid 549
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-
13.812548 methoxy-biphenyl-3-yl)-propionic acid 550
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.635486
amino}-3-(4-[1,2,4]triazol-1-yl-phenyl)-propionic acid 551
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.352071
amino}-3-(3-methoxy-biphenyl-4-yl)-propionic acid 552
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.323441
amino}-3-(4-methoxy-2-trifluoromethyl-phenyl)-propionic acid 553
3-(2-Fluoro-4-methoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5- 0.732366
hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 554
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 1.843808
amino}-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic acid 555
3-(2-Fluoro-4-methyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-hydroxy-
0.238578 1H-pyrazole-3-carbonyl]-amino}-propionic acid 556
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 8.652812
amino}-3-(4-methoxy-biphenyl-3-yl)-propionic acid 557
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.839178
amino}-3-(4-[1,2,4]triazol-1-yl-phenyl)-propionic acid 558
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.699161
amino}-3-(3-methoxy-biphenyl-4-yl)-propionic acid 559
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.731295
amino}-3-(2-fluoro-5-methoxy-phenyl)-propionic acid 560
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 7.623283
amino}-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic acid 561
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.265803
amino}-3-(2-fluoro-4-methyl-phenyl)-propionic acid 562
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 4.493781
amino}-3-(4-methoxy-biphenyl-3-yl)-propionic acid 563
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4- 1.74027
[1,2,4]triazol-1-yl-phenyl)-propionic acid 564
3-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.458522
pyrazole-3-carbonyl)-amino]-propionic acid 565
3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-
5.022589 pyrrolidin-1-yl-phenyl)-propionic acid 566
3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 2.986143
amino}-3-(4-pyrrolidin-1-yl-phenyl)-propionic acid 567
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 1.062689
amino}-3-(4-methoxy-2-trifluoromethyl-phenyl)-propionic acid 568
3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 2.354354
amino}-3-(4-pyrrolidin-1-yl-phenyl)-propionic acid 745
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl- 0.004703
butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 747
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-
0.014724 butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic
acid 748
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-
0.002558 butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic
acid 753
(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-
0.3449 hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-
propionic acid 758
(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2- 0.01742
hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-
amino}-propionic acid 766
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl- 0.000692
butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 768
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-
0.00115
2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid
771
(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-
0.00197 2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-
propionic acid 803
3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3- 0.0267
dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 860
(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl- 0.0761
butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 870
(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl- 0.076
butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid
* * * * *