U.S. patent application number 09/968042 was filed with the patent office on 2003-01-02 for azaindole derivatives, process for their preparation, and their use as antitumor agents.
This patent application is currently assigned to PHARMACIA & UPJOHN. Invention is credited to Brasca, Maria Gabriella, Longo, Antonio, Orsini, Paolo, Pevarello, Paolo, Pittala, Valeria, Traquandi, Gabriella, Varasi, Mario, Vulpetti, Anna.
Application Number | 20030004350 09/968042 |
Document ID | / |
Family ID | 24390825 |
Filed Date | 2003-01-02 |
United States Patent
Application |
20030004350 |
Kind Code |
A1 |
Longo, Antonio ; et
al. |
January 2, 2003 |
AZAINDOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION, AND THEIR USE
AS ANTITUMOR AGENTS
Abstract
Novel 1H-pyrrolo[2,3-b]pyridines which are represented by
formula (I): 1 wherein R is a hydrogen or halogen atom or a group
selected from --CN, --OH, --OCOR.sub.4, --(CH.sub.2).sub.nNH.sub.2,
--(CH.sub.2).sub.nNHR.sub- .4, --(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4, or
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is either 0 or 1,
R.sub.4 and R.sub.5 are as described in the specification; R.sub.1
is hydrogen or an optionally substituted alkyl group; R.sub.2 is an
optionally substituted group selected from alkyl or aryl; R.sub.3
is hydrogen or a group selected from --CONR.sub.4R.sub.5,
--COOR.sub.4, --CONHOR.sub.4, --SO.sub.2NHR.sub.4,
alkylsulphonylaminocarbonyl or perfluorinated
alkylsulphonylaminocarbonyl- ; or a pharmaceutically acceptable
salt thereof, are disclosed. These compounds are useful for
treating cell proliferative disorders associated with an altered
cell dependent kinase activity.
Inventors: |
Longo, Antonio; (Milan,
IT) ; Brasca, Maria Gabriella; (Cusago, IT) ;
Orsini, Paolo; (Gallarate, IT) ; Traquandi,
Gabriella; (Milan, IT) ; Pittala, Valeria;
(Catania, IT) ; Vulpetti, Anna; (Brugherio,
IT) ; Varasi, Mario; (Milan, IT) ; Pevarello,
Paolo; (Pavia, IT) |
Correspondence
Address: |
OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC
FOURTH FLOOR
1755 JEFFERSON DAVIS HIGHWAY
ARLINGTON
VA
22202
US
|
Assignee: |
PHARMACIA & UPJOHN
Milan
IT
|
Family ID: |
24390825 |
Appl. No.: |
09/968042 |
Filed: |
October 2, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09968042 |
Oct 2, 2001 |
|
|
|
09597274 |
Jun 19, 2000 |
|
|
|
6335342 |
|
|
|
|
Current U.S.
Class: |
546/113 |
Current CPC
Class: |
A61P 9/10 20180101; A61P
17/06 20180101; A61P 35/00 20180101; A61P 37/02 20180101; A61P
13/12 20180101; A61P 31/12 20180101; A61P 25/00 20180101; A61P
11/00 20180101; C07D 471/04 20130101; A61P 43/00 20180101; A61P
25/28 20180101; A61P 35/04 20180101; A61P 17/14 20180101; A61P
13/08 20180101 |
Class at
Publication: |
546/113 ;
514/300 |
International
Class: |
A61K 031/4745; C07D
471/02 |
Claims
1) A method for treating cell proliferative disorders associated
with an altered cell dependent kinase activity, by administering to
a mammal in need thereof an effective amount of a
1H-pyrrolo[2,3-b]pyridine represented by formula (I): 10wherein R
is a hydrogen or halogen atom or a group selected from --CN, --OH,
--OCOR.sub.4, --(CH.sub.2).sub.nNH.sub.- 2,
--(CH.sub.2).sub.nNHR.sub.4, --(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4, or
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is either 0 or 1,
R.sub.4 and R.sub.5 are, independently from each other, hydrogen or
an optionally substituted group selected from alkyl, alkenyl,
alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkylalkynyl, heterocyclyl, heterocyclylalkyl,
heterocyclylalkenyl, heterocyclylalkynyl, aryl, arylalkyl,
arylalkenyl, arylalkynyl or, taken together to the nitrogen atom to
which they are bonded, form an optionally substituted heterocyclyl
group such as pyrrolidine, piperidine, piperazine and morpholine;
R.sub.1 is hydrogen or an optionally substituted alkyl group;
R.sub.2 is an optionally substituted group selected from alkyl or
aryl; R.sub.3 is hydrogen or a group selected from
--CONR.sub.4R.sub.5, --COOR.sub.4, --CONHOR.sub.4,
--SO.sub.2NHR.sub.4, alkylsulphonylaminocarbonyl or perfluorinated
alkylsulphonylaminocarbonyl- ; wherein R.sub.4 and R.sub.5 have the
above reported meanings; or a pharmaceutically acceptable salt
thereof.
2) The method according to claim 1 wherein the cell proliferative
disorder is selected from the group consisting of cancer,
Alzheimer's disease, viral infections, auto-immune diseases and
neurodegenerative disorders.
3) The method according to claim 2 wherein the cancer is selected
from the group consisting of carcinoma, hematopoietic tumors of
lymphoid lineage, hematopoietic tumors of myeloid lineage, tumors
of mesenchymal origin, tumors of the central and peripheral nervous
system, melanoma, seminoma, teratocarcinoma, osteosarcoma,
xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer
and Kaposi's sarcoma.
4) The method according to claim 1 wherein the cell proliferative
disorder is selected from benign prostate hyperplasia, familial
adenomatosis polyposis, neuro-fibromatosis, psoriasis, vascular
smooth cell proliferation associated with atherosclerosis,
pulmonary fibrosis, arthritis glomerulonephritis and post-surgical
stenosis and restenosis.
5) The method according to claim 1 which provides tumor
angiogenesis and metastasis inhibition.
6) A 1H-pyrrolo{2,3-b]pyridine derivative represented by formula
(I): 11wherein R is a hydrogen or halogen atom or a group selected
from --CN, --OH, --OCOR.sub.4, --(CH.sub.2).sub.nNH.sub.2,
--(CH.sub.2).sub.nNHR.sub- .4, --(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4, or
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is either 0 or 1,
R.sub.4 and R.sub.5 are, independently from each other, hydrogen or
an optionally substituted group selected from alkyl, alkenyl,
alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkylalkynyl, heterocyclyl, heterocyclylalkyl,
heterocyclylalkenyl, heterocyclylalkynyl, aryl, arylalkyl,
arylalkenyl, arylalkynyl or, taken together to the nitrogen atom to
which they are bonded, form an optionally substituted heterocyclyl
group such as pyrrolidine, piperidine, piperazine and morpholine;
R.sub.1 is hydrogen or an optionally substituted alkyl group;
R.sub.2 is an optionally substituted group selected from alkyl or
aryl; R.sub.3 is hydrogen or a group selected from
--CONR.sub.4R.sub.5, --COOR.sub.4, --CONHOR.sub.4,
--SO.sub.2NHR.sub.4, alkylsulphonylaminocarbonyl or perfluorinated
alkylsulphonylaminocarbonyl; wherein R.sub.4 and R.sub.5 have the
above reported meanings; or a pharmaceutically acceptable salt
thereof.
7) A compound of formula (I) as defined in claim 6 wherein R is
hydrogen, halogen, cyano, hydroxy or a group --OCOR.sub.4,
--(CH.sub.2).sub.nNH.sub- .2, --(CH.sub.2).sub.nNHR.sub.4,
--(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4,
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is 0 or 1 and
R.sub.4 and R.sub.5 are, each independently, hydrogen or an
optionally substituted group selected from alkyl, heterocyclyl,
aryl or arylalkyl or, taken together to the nitrogen atom to which
they are bonded, R.sub.4 and R.sub.5 form an optionally substituted
pyrrolidino, piperidino, piperazino or morpholino group; and
R.sub.1, R.sub.2 and R.sub.3 have the meanings reported in claim
6.
8) A compound of formula (I) as defined in claim 7 wherein R.sub.3
is hydrogen or a group selected from --CONR.sub.4R.sub.5,
--COOR.sub.4 or --CONHOR.sub.4 wherein R.sub.4 and R.sub.5 are as
defined in claim 6.
9) A 1H-pyrrolo{2,3-b]pyridine derivative, optionally in the form
of a pharmaceutically acceptable salt, selected from the group
consisting of: 1.
3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
2.
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
3.
3-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
4.
3-(6-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
5.
3-(6-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
6.
3-(6-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
7.
3-[6-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide;
8.
3-{6-[(methylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-p-
ropenamide; 9.
3-{6-[(benzylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenamide; 10.
N-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-py-
rrolo[2,3-b]pyridin-6-yl}methyl)benzamide; 11.
2-phenyl-3-(6-{[(phenylacet-
yl)amino]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 12.
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl
benzoate; 13.
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-6-yl acetate; 14.
3-[6-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2--
phenyl-2-propenamide; 15.
3-[6-(ethylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-
-2-phenyl-2-propenamide; 16.
3-[6-(isopropylamino)-1H-pyrrolo[2,3-b]pyridi-
n-3-yl]-2-phenyl-2-propenamide; 17.
3-[6-(cyclohexylamino)-1H-pyrrolo[2,3--
b]pyridin-3-yl]-2-phenyl-2-propenamide; 18.
3-(6-anilino-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-2-phenyl-2-propenamide; 19.
3-[6-(4-bromoanilino)-1H-pyrrolo-
[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide; 20.
3-[6-(3-hydroxyanilino)-1-
H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide; 21.
3-{6-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-
-propenamide; 22.
4-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-
-b]pyridin-6-yl}amino)benzamide; 23.
3-[6-(3-aminoanilino)-1H-pyrrolo[2,3--
b]pyridin-3-yl]-2-propenamide; 24.
2-phenyl-3-[6-(3-pyridinylamino)-1H-pyr-
rolo[2,3-b]pyridin-3-yl]-2-propenamide; 25.
2-phenyl-3-[6-(1,3-thiazol-2-y-
lamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamide; 26.
3-[6-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide;
27.
3-(6-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide; 28.
3-[6-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3--
yl]-2-phenyl-2-propenamide; 29.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1-
H-pyrrolo[2,3-b]pyridin-6-yl}benzamide; 30.
N-{3-[3-amino-3-oxo-2-phenyl-1-
-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl)-4-bromobenzamide; 31.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl}-3-
-hydroxybenzamide; 32.
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-
-pyrrolo[2,3-b]pyridin-6-yl}benzamide; 33.
3-[6-(butyrylamino)-1H-pyrrolo[-
2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide; 34.
2-phenyl-3-{6-[(phenylacet-
yl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide; 35.
3-(6-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-ph-
enyl-2-propenamide; 36.
3-(6-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,-
3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 37.
3-(6-{[(3-aminophenyl)acetyl-
]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 38.
2-phenyl-3-{6-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenamide; 39.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3--
b]pyridin-6-yl}-1H-indole-3-carboxamide; 40.
3-{6-[(1H-indol-3-ylacetyl)am-
ino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 41.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl}-2-
-thiophenecarboxamide; 42.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyr-
rolo[2,3-b]pyridin-6-yl}[1,1'-biphenyl]-4-carboxamide; 43.
3-{6-[([1,1'-biphenyl]-4-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenamide; 44.
3-{6-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[-
2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 45.
2-phenyl-3-{6-[(1,3-thiazo-
l-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide;
46.
3-{6-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pro-
penamide; 47.
3-(6-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenamide; 48.
3-{6-[(anilinocarbonyl)amino]-1H-pyrrol-
o[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 49.
3-(6-{[(4-bromoanilino)c-
arbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
50.
3-(6-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-phenyl-2-propenamide; 51.
3-(6-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 52.
N-(3-[3-amino-3-oxo-2-phen-
yl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl}-1-piperidinecarboxamide;
53.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl}-4-
-methyl-1-piperazinecarboxamide; 54.
N-{3-[3-amino-3-oxo-2-phenyl-1-propen-
yl]-1H-pyrrolo[2,3-b]pyridin-6-yl}-4-morpholinecarboxamide; 55.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl}-1-
H-pyrrolidinecarboxamide; 56. ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]--
1H-pyrrolo[2,3-b]pyridin-6-ylcarbamate; 57. tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-ylcarbam-
ate; 58.
3-{6-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phe-
nyl-2-propenamide; 59.
2-phenyl-3-{6-[(phenylsulfonyl)amino]-1H-pyrrolo[2,-
3-b]pyridin-3-yl}-2-propenamide; 60.
2-phenyl-3-(6-{[(phenylsulfonyl)methy-
l]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 61.
3-(6-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenamide; 62.
3-{6-[([1,1'-biphenyl]-4-ylsulfonyl)a-
mino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 63.
3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
64.
3-(4-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
65.
3-[4-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenami-
de; 66.
3-[4-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenamide; 67.
3-{4-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin--
3-yl}-2-phenyl-2-propenamide; 68.
4-({3-[3-amino-3-oxo-2-phenyl-1-propenyl-
]-1H-pyrrolo[2,3-b]pyridin-4-yl}amino)benzamide; 69.
3-[4-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenami-
de; 70.
2-phenyl-3-[4-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2--
propenamide; 71.
2-phenyl-3-[4-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]py-
ridin-3-yl]-2-propenamide; 72.
3-(4-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2- -phenyl-2-propenamide;
73. 3-[4-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-y-
l]-2-phenyl-2-propenamide; 74.
3-[4-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyr-
idin-3-yl]-2-phenyl-2-propenamide; 75.
3-[4-(benzylamino)-1H-pyrrolo[2,3-b-
]pyridin-3-yl]-2-phenyl-2-propenamide; 76.
3-(4-{[4-(aminosulfonyl)benzyl]-
amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 77.
3-[4-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide;
78.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-y-
l}benzamide; 79.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b-
]pyridin-4-yl}-4-bromobenzamide; 80.
N-{3-[3-amino-3-oxo-2-phenyl-1-propen-
yl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-3-hydroxybenzamide; 81.
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-
-4-yl}benzamide; 82.
3-[4-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2--
phenyl-2-propenamide; 83.
2-phenyl-3-{4-[(phenylacetyl)amino]-1H-pyrrolo[2-
,3-b]pyridin-3-yl}-2-propenamide; 84.
3-(4-{[(3-hydroxyphenyl)acetyl]amino-
}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 85.
3-(4-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phe-
nyl-2-propenamide; 86.
3-(4-([(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-phenyl-2-propenamide; 87.
2-phenyl-3-{4-[(3-pyridinylace-
tyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide; 88.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1-
H-indole-3-carboxamide; 89.
3-{4-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2-
,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 90.
N-{3-[3-amino-3-oxo-2-pheny-
l-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-2-thiophenecarboxamide;
91.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}[1-
,1'-biphenyl]-4-carboxamide; 92.
3-{4-[(1,3-oxazol-2-ylacetyl)amino]-1H-py-
rrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 93.
2-phenyl-3-{4-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl}-2-propenamide; 94.
3-{4-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridi-
n-3-yl}-2-phenyl-2-propenamide; 95.
3-(4-{[(methylamino)carbonyl]amino}-1H-
-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 96.
3-{4-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-p-
ropenamide; 97.
3-(4-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-phenyl-2-propenamide; 98.
3-(4-{[(3-hydroxyanilino)carbonyl]-
amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 99.
3-(4-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phen-
yl-2-propenamide; 100.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo-
[2,3-b]pyridin-4-yl}-1-piperidinecarboxamide; 101.
N-{3-[3-amino-3-oxo-2-p-
henyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1-pyrrolidinecarboxamide;
102.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4--
yl}-4-methyl-1-piperazinecarboxamide; 103.
N-{3-[3-amino-3-oxo-2-phenyl-1--
propenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-4-morpholinecarboxamide;
104. 1-ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4--
ylcarbamate; 105. 1-tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-py-
rrolo[2,3-b]pyridin-4-ylcarbamate; 106.
3-{4-[(methylsulfonyl)amino]-1H-py-
rrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 107.
2-phenyl-3-{4-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pr-
openamide; 108.
3-{4-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-phenyl-2-propenamide; 109.
3-{4-[([1,1'-biphenyl]-4-ylsulfonyl)amino]--
1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 110.
3-(4-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenamide; 111.
3-(5-amino-1H-pyrrolo[2,3-b]pyridin-- 3-yl)-2-phenyl-2-propenamide;
112. 3-[5-(methylamino)-1H-pyrrolo[2,3-b]pyr-
idin-3-yl]-2-phenyl-2-propenamide; 113.
3-[5-(cyclohexylamino)-1H-pyrrolo[-
2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide; 114.
3-[5-(benzylamino)-1H-pyr-
rolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide; 115.
3-(5-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-ph-
enyl-2-propenamide; 116.
3-[5-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-
-2-phenyl-2-propenamide; 117.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H--
pyrrolo[2,3-b]pyridin-5-yl}benzamide; 118.
N-{3-[3-amino-3-oxo-2-phenyl-1--
propenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-4-bromobenzamide; 119.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-3-
-hydroxybenzamide; 120.
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1-
H-pyrrolo[2,3-b]pyridin-5-yl}benzamide; 121.
3-[5-(butyrylamino)-1H-pyrrol-
o[2,3-b]pyridin-3-yl]-2-phenyl-2-propenamide; 122.
2-phenyl-3-{5-[(phenyla-
cetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide; 123.
3-(5-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-ph-
enyl-2-propenamide; 124.
3-(5-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2-
,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 125.
3-(5-{[(3-aminophenyl)acet-
yl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
126.
2-phenyl-3-{5-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenamide; 127.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-
-b]pyridin-5-yl}-1H-indole-3-carboxamide; 128.
3-{5-[(1H-indol-3-ylacetyl)-
amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 129.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-2-
-thiophenecarboxamide; 130.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-py-
rrolo[2,3-b]pyridin-5-yl}[1,1'-biphenyl]-4-carboxamide; 131.
3-{5-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenamide; 132.
2-phenyl-3-{5-[(1,3-thiazol-2-ylacetyl)amino]-1H
pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide; 133.
3-{5-[(aminocarbonyl)amin-
o]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 134.
3-(5-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phen-
yl-2-propenamide; 135.
3-{5-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-phenyl-2-propenamide; 136.
3-(5-{[(4-bromoanilino)carbonyl]ami-
no}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 137.
3-(5-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-phenyl-2-propenamide; 138.
3-(5-{[(benzylamino)carbonyl]amino}-1H-pyrrolo-
[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 139.
N-{3-[3-amino-3-oxo-2-ph-
enyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-piperidinecarboxamide;
140.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5--
yl}-1-pyrrolidinecarboxamide; 141.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl-
]-1H-pyrrolo[2,3-b]pyridin-5-yl}-4-methyl-1-piperazinecarboxamide;
142.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-4-
-morpholinecarboxamide; 143. ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1-
H-pyrrolo[2,3-b]pyridin-5-ylcarbamate; 144. tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-ylcarbam-
ate; 145.
3-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenamide; 146.
2-phenyl-3-{5-[(phenylsulfonyl)amino]-1H-pyrrolo[-
2,3-b]pyridin-3-yl}-2-propenamide; 147.
3-{5-[(benzylsulfonyl)amino]-1H-py-
rrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenamide; 148.
3-{5-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-
-2-phenyl-2-propenamide; 149.
3-(5-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]-
amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 150.
3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 151.
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 152.
3-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoi- c
acid; 153.
3-(6-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoi- c
acid; 154.
3-(6-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoi- c
acid; 155.
3-(6-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propen- oic
acid; 156.
3-[6-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenoic acid; 157.
3-{6-[(methylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid; 158.
3-{6-[(benzylamino)methyl]-1H-pyrro-
lo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 159.
3-{6-[(benzoylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pro-
penoic acid; 160.
2-phenyl-3-(6-{[(phenylacetyl)amino]methyl}-1H-pyrrolo[2-
,3-b]pyridin-3-yl)-2-propenoic acid; 161.
3-[6-(benzoyloxy)-1H-pyrrolo[2,3-
-b]pyridin-3-yl]-2-phenyl-2-propenoic acid; 162.
3-[6-(acetyloxy)-1H-pyrro-
lo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic acid; 163.
3-[6-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic
acid; 164.
3-[6-(ethylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openoic acid; 165.
3-[6-(isopropylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2--
phenyl-2-propenoic acid; 166.
3-[6-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyri- din-3-yl]-2-phenyl-2-
propenoic acid; 167. 3-(6-anilino-1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-phenyl-2-propenoic acid; 168.
3-[6-(4-bromoanilino)-1H-pyrr- olo[2,3-b]pyridin-3-yl]-2-phenyl-2-
propenoic acid; 169.
3-[6-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
propenoic acid; 170.
3-{6-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyr-
idin-3-yl}-2-phenyl-2-propenoic acid; 171.
3-{6-[4-(aminocarbonyl)anilino]-
-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 172.
3-[6-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenoic
acid; 173.
2-phenyl-3-[6-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-
propenoic acid; 174.
2-phenyl-3-[6-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-
-b]pyridin-3-yl]-2-propenoic acid; 175.
3-[6-(benzylamino)-1H-pyrrolo[2,3--
b]pyridin-3-yl]-2-phenyl-2-propenoic acid; 176.
3-(6-{[4-(aminosulfonyl)be-
nzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 177.
3-[6-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic
acid; 178.
3-[6-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid; 179.
3-{6-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid; 180.
3-{6-[(3-hydroxybenzoyl)amino]-1H-p-
yrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 181.
3-{6-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pr-
openoic acid; 182.
3-[6-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-ph-
enyl-2-propenoic acid; 183.
2-phenyl-3-{6-[(phenylacetyl)amino]-1H-pyrrolo-
[2,3-b]pyridin-3-yl}-2-propenoic acid; 184.
3-(6-{[(3-hydroxyphenyl)acetyl-
]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
185.
3-(6-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phe-
nyl-2-propenoic acid; 186.
3-(6-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 187.
2-phenyl-3-{6-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenoic acid; 188.
3-{6-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-phenyl-2-propenoic acid; 189.
3-{6-[(1H-indol-3-ylacetyl)-
amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid;
190.
2-phenyl-3-{6-[(2-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenoic acid; 191.
3-{6-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrol-
o[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 192.
3-{6-[([1,1'-biphenyl]-4-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenoic acid; 193.
3-{6-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrr-
olo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 194.
2-phenyl-3-{6-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl}-2-propenoic acid; 195.
3-{6-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid; 196.
3-(6-{[(methylamino)carbonyl]a-
mino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
197.
3-{6-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-p-
ropenoic acid; 198.
3-(6-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 199.
3-(6-{[(3-hydroxyanilino)c-
arbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 200.
3-(6-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-phenyl-2-propenoic acid; 201.
2-phenyl-3-{6-[(1-piperidinylcarbonyl)amino-
]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic acid; 202.
2-phenyl-3-{6-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl}-2-propenoic acid; 203.
3-(6-{[(4-methyl-1-piperazinyl)carbonyl]amino}--
1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 204.
3-{6-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenoic acid; 205.
3-{6-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid; 206.
3-{6-[(tert-butoxycarbonyl)ami-
no]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 207.
3-{6-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pr-
openoic acid; 208.
2-phenyl-3-{6-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]-
pyridin-3-yl}-2-propenoic acid; 209.
2-phenyl-3-(6-{[(phenylsulfonyl)methy-
l]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 210.
3-(6-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenoic acid; 211.
3-{6-[([1,1'-biphenyl]-4-ylsulfon-
yl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid;
212.
3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 213.
3-(4-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 214.
3-[4-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenoic acid; 215.
3-[4-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3--
yl]-2-phenyl-2-propenoic acid; 216.
3-{4-[4-(aminosulfonyl)anilino]-1H-pyr-
rolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 217.
3-{4-[4-(aminocarbonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-
-propenoic acid; 218.
3-[4-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-
-2-phenyl-2-propenoic acid; 219.
2-phenyl-3-[4-(3-pyridinylamino)-1H-pyrro-
lo[2,3-b]pyridin-3-yl]-2-propenoic acid; 220.
2-phenyl-3-[4-(1,3-thiazol-2-
-ylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenoic acid; 221.
3-(4-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid; 222.
3-[4-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--2-propenoic
acid; 223.
3-[4-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-
-2-propenoic acid; 224.
3-[4-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]--
2-phenyl--2-propenoic acid; 225.
3-(4-{[4-(aminosulfonyl)benzyl]amino}-1H--
pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 226.
3-[4-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--2-propenoic
acid; 227.
3-[4-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid; 228.
3-{4-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid; 229.
3-{4-[(3-hydroxybenzoyl)amino]-1H-p-
yrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 230.
3-{4-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pr-
openoic acid; 231.
3-[4-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-ph-
enyl-2-propenoic acid; 232.
2-phenyl-3-{4-[(phenylacetyl)amino]-1H-pyrrolo-
[2,3-b]pyridin-3-yl}-2-propenoic acid; 233.
3-(4-{[(3-hydroxyphenyl)acetyl-
]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
234.
3-(4-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phe-
nyl-2-propenoic acid; 235.
3-(4-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 236.
2-phenyl-3-{4-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenoic acid; 237.
3-{4-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-phenyl-2-propenoic acid; 238.
3-{4-[(1H-indol-3-ylacetyl)-
amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid;
239.
2-phenyl-3-{4-[(3-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenoic acid; 240.
3-{4-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrol-
o[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 241.
3-{4-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenoic acid; 242.
2-phenyl-3-{4-[(1,3-thiazol-2-ylacetyl)amino]-1H-
-pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic acid; 243.
3-{4-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pro-
penoic acid; 244.
3-(4-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-phenyl-2-propenoic acid; 245.
3-{4-[(anilinocarbonyl)amino]-1-
H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 246.
3-(4-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
henyl-2-propenoic acid; 247.
3-(4-{[(3-hydroxyanilino)carbonyl]amino}-1H-p-
yrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 248.
3-(4-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phen-
yl-2-propenoic acid; 249.
2-phenyl-3-{4-[(1-piperidinylcarbonyl)amino]-1H--
pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic acid; 250.
2-phenyl-3-{4-[(1-pyrro-
lidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic
acid; 251.
3-(4-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-phenyl-2-propenoic acid; 252. 3-{4-[(4-morpholinyl
arbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic
acid; 253.
3-{4-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenoic acid; 254.
3-{4-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-phenyl-2-propenoic acid; 255.
3-{4-[(methylsulfonyl)amino-
]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 256.
2-phenyl-3-{4-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pr-
openoic acid; 257.
3-{4-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid; 258.
3-{4-[([1,1'-biphenyl]-4-ylsulfonyl)a-
mino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid;
259.
3-(4-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenoic acid; 260.
3-(5-amino-1H-pyrrolo[2,3-b]pyrid- in-3-yl)-2-phenyl-2-propenoic
acid; 261. 3-[5-(methylamino)-1H-pyrrolo[2,3-
-b]pyridin-3-yl]-2-phenyl-2-propenoic acid; 262.
3-[5-(cyclohexylamino)-1H-
-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic acid; 263.
3-[5-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic
acid; 264.
3-(5-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid; 265.
3-[5-(acetylamino)-1H-pyrrolo[2,3-b-
]pyridin-3-yl]-2-phenyl-2-propenoic acid; 266.
3-[5-(benzoylamino)-1H-pyrr-
olo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic acid; 267.
3-{5-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pr-
openoic acid; 268.
3-{5-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid; 269.
3-{5-[(3-aminobenzoyl)amino]-1H-pyr-
rolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 270.
3-[5-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoic
acid; 271.
2-phenyl-3-{5-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid; 272.
3-(5-{[(3-hydroxyphenyl)acetyl]amino)-1H-pyrro-
lo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 273.
3-(5-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phe-
nyl-2-propenoic acid; 274.
3-(5-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 275.
2-phenyl-3-{5-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenoic acid; 276.
3-{5-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-phenyl-2-propenoic acid; 277.
3-(5-[(1H-indol-3-ylacetyl)-
amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid;
278.
2-phenyl-3-{5-[(3-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-propenoic acid; 279.
(2E)-3-{5-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-p-
yrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 280.
3-{5-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenoic acid; 281.
2-phenyl-3-{5-[(1,3-thiazol-2-ylacetyl)amino]-1H-
-pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic acid; 282.
3-{5-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pro-
penoic acid; 283.
3-(5-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-phenyl-2-propenoic acid; 284.
3-{5-[(anilinocarbonyl)amino]-1-
H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 285.
3-(5-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
henyl-2-propenoic acid; 286.
3-(5-{[(3-hydroxyanilino)carbonyl]amino}-1H-p-
yrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid; 287.
3-(5-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phen-
yl-2-propenoic acid; 288.
2-phenyl-3-{5-[(1-piperidinylcarbonyl)amino]-1H--
pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic acid; 289.
2-phenyl-3-{5-[(1-pyrro-
lidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenoic
acid; 290.
3-(5-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-phenyl-2-propenoic acid; 291.
3-{5-[(4-morpholinylcarbonyl)ami-
no]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 292.
3-{5-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-pr-
openoic acid; 293.
3-{5-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-phenyl-2-propenoic acid; 294.
3-{5-[(methylsulfonyl)amino]-1H--
pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid; 295.
2-phenyl-3-{5-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pr-
openoic acid; 296.
3-{5-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid; 297.
3-{5-[([1,1'-biphenyl]-4-ylsulfonyl)a-
mino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-2-propenoic acid;
298.
3-(5-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenoic acid; 299.
2-phenyl-3-(1H-pyrrolo[2,3-b]pyri- din-3-yl)-2-propenamide; 300.
2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2- -propenoic acid; 301.
N-butyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2- -propenamide;
302. 2-(4-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenoic acid; 303.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(4-tolyl)-2-prope- noic acid;
304. 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[2-(trifluoromethyl)ph-
enyl]-2-propenoic acid; 305.
2-(1-acetyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-propenoic acid; 306.
2-(1H-indol-3-yl)-3-(1H-pyrrolo[2,3- -b]pyridin-3-yl)-2-propenoic
acid; 307. 2-(3-fluoro-4-hydroxyphenyl)-3-(1H-
-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 308.
2-(2,3-dihydro-1H-inden-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno-
ic acid; 309.
2-(3-pyridinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi- c
acid; 310.
2-(4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope- noic
acid; 311.
2-(4-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr- openoic
acid; 312. 2-(2-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenoic acid; 313.
2-(2-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl- )-2-propenoic
acid; 314. 2-[1,1'-biphenyl]-4-yl-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenoic acid; 315.
2-(4-hydroxy-5-isopropyl-2-methylphenyl)-3--
(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 316.
2-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno-
ic acid; 317.
2-(3-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope- noic
acid; 318.
2-(3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr- openoic
acid; 319. 2-(3-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenoic acid; 320.
2-(1,3-benzodioxol-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-propenoic acid; 321.
2-(3,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenoic acid; 322.
2-(3-fluorophenyl)-3-(1H-pyrrolo[2,3-b]- pyridin-3-yl)-2-propenoic
acid; 323. 2-(4-butoxyphenyl)-3-(1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-propenoic acid; 324.
2-(3-chloro-4-hydroxyphenyl)-3-(1H--
pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 325.
2-[4-(methylsulfonyl)ph-
enyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 326.
2-(4-ethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid; 327.
2-(3-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid; 328.
2-(2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid; 329.
2-(3,4-dihydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenoic acid; 330.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(2-thienyl)-2-pro- penoic acid;
331. 2-(2-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid; 332.
2-(2-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-- propenoic
acid; 333. 2-(2-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenoic acid; 334.
2-(2,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenoic acid; 335.
2-(2-chloro-6-fluorophenyl)-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenoic acid; 336.
2-(2,6-dichlorophenyl)-3-(1H-pyrro-
lo[2,3-b]pyridin-3-yl)-2-propenoic acid; 337.
2-(2,5-dimethoxyphenyl)-3-(1-
H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 338.
2-(3,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)
-2-propenoic acid; 339.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3,4,5-trimethoxyphenyl)-2-
-propenoic acid; 340.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[3-(trifluoromet-
hyl)phenyl]-2-propenoic acid; 341.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4--
(trifluoromethyl)phenyl]-2-propenoic acid; 342.
2-[3,5-bis(trifluoromethyl-
)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 343.
2-(2,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid; 344.
2-(2,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid; 345.
2-(3,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid; 346.
2-(3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenoic acid; 347.
2-[4-(benzyloxy)-3-methoxyphenyl]-3-(1H-pyrr-
olo[2,3-b]pyridin-3-yl)-2-propenoic acid; 348.
3-(1H-pyrrolo[2,3-b]pyridin- -3-yl)-2-(3-thienyl)-2-propenoic acid;
349. 2-(5-methoxy-1H-indol-3-yl)-3--
(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 350.
2-(1-naphthyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid;
351.
2-(3-methyl-1-benzothien-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
oic acid; 352.
2-(3,4-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenoic acid; 353.
2-(4-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-- 2-propenoic
acid; 354. 2-[4-(acetylamino)phenyl]-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenoic acid; 355.
2-[4-amino-phenyl]-3-(1H-pyrrolo[2,3-b]pyr- idin-3-yl)-2-propenoic
acid; 356. 2-(5-bromo-1H-indol-3-yl)-3-(1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-propenoic acid; 357.
2-(1-methyl-1H-indol-3-yl)-3-(1-
H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 358.
2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid; 359.
2-[2,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid; 360.
2-(2,3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenoic acid; 361.
2-[5-(benzyloxy)-1H-indol-3-yl]-3-(1H-pyrr-
olo[2,3-b]pyridin-3-yl)-2-propenoic acid; 362.
2-(2-amino-1,3-thiazol-4-yl-
)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 363.
2-mesityl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 364.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethoxy)phenyl]-2-propen-
oic acid; 365.
2-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenoic acid; 366.
2-[4-(2-amino-2-oxoethoxy)phenyl]-3-(1H-
-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 367.
2-{4-[2-oxo-2-(1-pyrrolidinyl)ethoxy]phenyl}-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenoic acid; 368.
2-(3-hydroxy-5-methoxy-2-propylphenyl)-3-(1H--
pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 369.
2-(4-phenoxyphenyl)-3-(- 1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid; 370.
2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid; 371.
2-{3-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-propenoic acid; 372.
2-{4-[(methylsulfonyl)amino]phe-
nyl}-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic acid; 373.
2-[4-(1-pyrrolidinyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid; 374.
2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenoic acid; 375.
2-(4-chlorophenyl)-3-(1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-propenamide; 376.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(4-- tolyl)-2-propenamide; 377.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[2-(trifluo-
romethyl)phenyl]-2-propenamide; 378.
2-(1-acetyl-1H-indol-3-yl)-3-(1H-pyrr-
olo[2,3-b]pyridin-3-yl)-2-propenamide; 379.
2-(1H-indol-3-yl)-3-(1H-pyrrol-
o[2,3-b]pyridin-3-yl)-2-propenamide; 380.
2-(3-fluoro-4-hydroxyphenyl)-3-(-
1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 381.
2-(2,3-dihydro-1H-inden-
-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 382.
2-(3-pyridinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
383.
2-(4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
384.
2-(4-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
385.
2-(2-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
386.
2-(2-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
387.
2-[1,1'-biphenyl]-4-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
388.
2-(4-hydroxy-5-isopropyl-2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenamide; 389.
2-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenamide; 390.
2-(3-chlorophenyl)-3-(1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-propenamide; 391.
2-(3-methoxyphenyl)-3-(1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-propenamide; 392.
2-(3-bromophenyl)-3-(1H-pyrrolo[2,3-b]-
pyridin-3-yl)-2-propenamide; 393.
2-(1,3-benzodioxol-5-yl)-3-(1H-pyrrolo[2-
,3-b]pyridin-3-yl)-2-propenamide; 394.
2-(3,5-dimethoxyphenyl)-3-(1H-pyrro- lo[2,3-b]pyridin-3-yl)
-2-propenamide; 395. 2-(3-fluorophenyl)-3-(1H-pyrro-
lo[2,3-b]pyridin-3-yl)-2-propenamide; 396.
2-(4-butoxyphenyl)-3-(1H-pyrrol-
o[2,3-b]pyridin-3-yl)-2-propenamide; 397.
2-(3-chloro-4-hydroxyphenyl)-3-(-
1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 398.
2-[4-(methylsulfonyl)ph-
enyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 399.
2-(4-ethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
400.
2-(3-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
401.
2-(2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
402.
2-(3,4-dihydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
403. 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(2-thienyl)-2-propenamide;
404.
2-(2-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
405.
2-(2-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
406.
2-(2-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
407.
2-(2,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
408.
2-(2-chloro-6-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enamide; 409.
2-(2,6-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenamide; 410.
2-(2,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide; 411.
2-(3,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenamide; 412.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3,4,5-trimeth-
oxyphenyl)-2-propenamide; 413.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[3-(tri-
fluoromethyl)phenyl]-2-propenamide; 414.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-[4-(trifluoromethyl)phenyl]-2-propenamide; 415.
2-[3,5-bis(trifluoromet-
hyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 416.
2-(2,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
417.
2-(2,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenami-
de; 418.
2-(3,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide; 419.
2-(3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide; 420.
2-[4-(benzyloxy)-3-methoxyphenyl]-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenamide; 421.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3-thieny- l)-2-propenamide;
422. 2-(5-methoxy-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-propenamide; 423.
2-(1-naphthyl)-3-(1H-pyrrolo[2,3-b]pyridin-- 3-yl)-2-propenamide;
424. 2-(3-methyl-1-benzothien-2-yl)-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenamide; 425.
2-(3,4-dimethoxyphenyl)-3-(1H-pyrrolo-
[2,3-b]pyridin-3-yl)-2-propenamide; 426.
2-(4-bromophenyl)-3-(1H-pyrrolo[2-
,3-b]pyridin-3-yl)-2-propenamide; 427.
2-[4-(acetylamino)phenyl]-3-(1H-pyr-
rolo[2,3-b]pyridin-3-yl)-2-propenamide; 428.
2-[4-amino-phenyl]-3-(1H-pyrr-
olo[2,3-b]pyridin-3-yl)-2-propenamide; 429. 2-
(5-bromo-H-indol-3-yl)-3-(1-
H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 430.
2-(1-methyl-1H-indol-3-y-
l)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 431.
2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
432.
2-[2,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide; 433.
2-(2,3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide; 434.
2-[5-(benzyloxy)-1H-indol-3-yl]-3-(1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenamide; 435.
2-(2-amino-1,3-thiazol-4-yl)-3-(1H-pyrrol-
o[2,3-b]pyridin-3-yl)-2-propenamide; 436.
2-mesityl-3-(1H-pyrrolo[2,3-b]py- ridin-3-yl)-2-propenamide; 437.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(tr-
ifluoromethoxy)phenyl]-2-propenamide; 438.
2-(3,5-ditert-butyl-4-hydroxyph-
enyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 439.
2-[4-(2-amino-2-oxoethoxy)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide; 440.
2-{4-[2-oxo-2-(1-pyrrolidinyl)ethoxy]phenyl}-3-(1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-propenamide; 441.
2-(3-hydroxy-5-methoxy-2-propylphe-
nyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 442.
2-(4-phenoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
443.
2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide; 444.
2-{3-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenamide; 445.
2-{4-[(methylsulfonyl)amino]phenyl}-3-
-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 446.
2-[4-(1-pyrrolidinyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide; 447.
2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-propenamide; 448.
N-benzyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide; 449.
N-(4-methoxyphenyl)-2-phenyl-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenamide; 450.
1-(4-morpholinyl)-2-phenyl-3-(1H-pyrr-
olo[2,3-b]pyridin-3-yl)-2-propen-1-one 451.
N-(4-chlorophenyl)-2-phenyl-3--
(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 452.
N,N-dimethyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
453.
N-isopropyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide-
; 454.
2-phenyl-1-(1-piperidinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
en-1-one 455.
N-[(3-aminomethyl)-pyridin]-2-phenyl-3-(1H-pyrrolo[-2,3-b]py-
ridin-3-yl)-2-propenamide; 456.
N-benzyl-N-methyl-2-phenyl-3-(1H-pyrrolo[2-
,3-b]pyridin-3-yl)-2-propenamide; 457.
N-(1H-indazol-6-yl)-2-phenyl-3-(1H--
pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 458.
N-(4-methoxybenzyl)-2-phen-
yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 459.
N-(4-chlorobenzyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenami-
de; 460.
N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-phenyl-3-(1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenamide; 461.
N-furfuryl-2-phenyl-3-(1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenamide; 462.
N-(4-hydroxypiperidin)-2-phenyl-3-(1H-pyr-
rolo[2,3-b]pyridin-3-yl)-2-propenamide; 463.
N-(3-hydroxypiperidin)-2-phen-
yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 464.
N-(3-methoxyphenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide; 465.
N,2-diphenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 466.
3-[3-(4-methyl-1-piperazinyl)-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[-
2,3-b]pyridine 467.
N-[4-(dimethylamino)phenyl]-2-phenyl-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenamide; 468.
N-(3-chlorophenyl)-2-phenyl-3-(1H-pyr-
rolo[2,3-b]pyridin-3-yl)-2-propenamide; 469.
N,N-diethyl-2-phenyl-3-(1H-py-
rrolo[2,3-b]pyridin-3-yl)-2-propenamide; 470.
3-[3-(4-benzyl-1-piperazinyl-
)-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridine 471.
2-[2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoyl]-1,2,3,4-tetrah-
ydroisoquinoline 472.
N-(tert-butoxy)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenamide; and 473.
N-hydroxy-2-phenyl-3-(1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-propenamide; 474.
N-methyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide; 475.
3-{6-[(2-naphthylacetyl)amino]-1H-pyrrolo[2,3--
b]pyridin-3-yl}-2-phenyl-2-propenamide; 476.
2-(3-chloro-4-hydroxyphenyl)--
3-{6-[(2-naphthylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamid-
e; 477.
3-{6-[(1-naphthylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenamide; 478.
2-(3-chloro-4-hydroxyphenyl)-3-{6-[(1-naphthylace-
tyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide; 479.
2-phenyl-3-[6-({[4-(2-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[2,3-b]pyrid-
in-3-yl]-2-propenamide; 480.
2-(3-chloro-4-hydroxyphenyl)-3-[6-({[4-(2-thi-
enyl)phenyl]acetyl}amino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamide;
481.
2-phenyl-3-[6-({[4-(3-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[2,3-b]-
pyridin-3-yl]-2-propenamide; 482.
2-(3-chloro-4-hydroxyphenyl)-3-[6-({[4-(-
3-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamid-
e; 483. 3-(6-{[(3',4'-difluoro[1,1'-biphenyl]-4-20
yl)acetyl]amino}-1H-pyr-
rolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 484.
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(3',4'-difluoro[1,1'-biphenyl]-4-yl)a-
cetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide; 485.
3-(6-{[(5'-fluoro-2'-methoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo-
[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide; 486.
2-(3-chloro-4-hydroxyphe-
nyl)-3-(6-{[(5'-fluoro-2'-methoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyr-
rolo[2,3-b]pyridin-3-yl)-2-propenamide; 487.
3-(6-{[(2',5'-difluoro[1,1'-b-
iphenyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-prop-
enamide; 488.
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(2',5'-difluoro[1,1'-bip-
henyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
489.
3-(6-{[(3'-ethoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenamide; 490.
2-(3-chloro-4-hydroxyphenyl)-3-
-(6-{[(3'-ethoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide.
10) A process for preparing the compounds of formula (I) according
to claim 6, or the pharmaceutically acceptable salts thereof,
comprising reacting a compound of formula (II) 12wherein R and
R.sub.1 are as defined in claim 6, with a compound of formula (III)
13wherein R.sub.2 is as defined in claim 6 and X represents a
hydrogen atom, a --COOH carboxy group or a derivative thereof such
as --COOR.sub.4 or --CONR.sub.4R.sub.5, wherein R.sub.4 and R.sub.5
are as defined in claim 6, thus obtaining a compound of formula (I)
wherein R, R.sub.1 and R.sub.2 are as defined above and R.sub.3 is
a hydrogen atom, a --COOH carboxy group or a derivative thereof
such as --COOR.sub.4 or --CONR.sub.4R.sub.5; and, if desired,
converting the said compound of formula (I) into another compound
of formula (I) and/or into a salt thereof.
11) The process of claim 10 for preparing a compound of formula (I)
as defined in claim 6 wherein R.sub.3 is a COOH carboxy group which
comprises reacting a compound of formula (II) with a compound of
formula (III) wherein X is hydrogen.
12) The process of claim 10 for preparing a compound of formula (I)
as defined in claim 6 wherein R.sub.3 is hydrogen, which process
comprises reacting a compound of formula (II) with a compound of
formula (III) wherein X is a --COOH carboxy group.
13) The process of claim 10 for preparing a compound of formula (I)
as defined in claim 6 wherein R.sub.3 is a carboxy derivative such
as --CONR.sub.4R.sub.5 or --COOR.sub.4, which process comprises
reacting a compound of formula (II) with a compound of formula
(III) wherein X is a --CONR.sub.4R.sub.5 or --COOR.sub.4 group.
14) A compound of formula (II) 14wherein R is a halogen atom or a
group selected from --CN, --OH, --OCOR.sub.4,
--(CH.sub.2).sub.nNH.sub.2, --(CH.sub.2).sub.nNHR.sub.4,
--(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4, or
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is either 0 or 1,
R.sub.4 and R.sub.5 are, independently from each other, hydrogen or
an optionally substituted group selected from alkyl, alkenyl,
alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkylalkynyl, heterocyclyl, heterocyclylalkyl,
heterocyclylalkenyl, heterocyclylalkynyl, aryl, arylalkyl,
arylalkenyl, arylalkynyl or, taken together to the nitrogen atom to
which they are bonded, form an optionally substituted heterocyclyl
group such as pyrrolidine, piperidine, piperazine and morpholine;
and R.sub.1 is hydrogen or an optionally substituted alkyl
group.
15) A process for preparing a compound of formula (II) as defined
in claim 14, wherein R.sub.1 is hydrogen, which process comprises
reacting a compound of formula (VII) 15wherein R is as defined in
claim 14, with a suitable formylating agent such as
hexamethylenetetramine.
16) A process for preparing a compound of formula (II) as defined
in claim 14, wherein R.sub.1 is alkyl, which process comprises
reacting a compound of formula (VII), as defined in claim 15, with
a) methylmagnesium iodide, thus obtaining a compound of formula
(VIII) 16b) reacting the compound of formula (VIII) with a compound
of formula (IX) R.sub.1COCl (IX) wherein R.sub.1 is an alkyl group
optionally substituted as defined in claim 14, thus obtaining a
compound of formula (X) 17wherein R and R.sub.1 are as def ined
above; and c) hydrolyzing the compound of formula (X) in the
presence of a base.
17) A pharmaceutical composition comprising the
1H-pyrrolo[2,3-b]pyridine derivative of formula (I) according to
claim 6 and at least one pharmaceutically acceptable carrier and/or
diluent.
Description
[0001] The present invention relates to azaindole derivatives and,
more in particular, to 1H-pyrrolo[2,3-b]pyridine derivatives, to a
process for their preparation, to pharmaceutical compositions
comprising them and to their use as therapeutic agents,
particularly in the treatment of cancer and cell proliferative
disorders.
[0002] Several cytotoxic drugs such as, e.g. fluorouracil (5-FU),
doxorubicin and camptothecins result to damage DNA or to affect
cellular metabolic pathways and thus cause, in many cases, an
indirect block of the cell cycle. Therefore, by producing an
irreversible damage to both normal and tumor cells, these agents
result in a significant toxicity and side-effects.
[0003] In this respect, compounds capable of being highly specific
antitumor agents by selectively leading to tumor cell arrest and
apoptosis, with comparable efficacy but reduced toxicity than the
currently available drugs, are desirable. It is well known in the
art that progression through the cell cycle is governed by a series
of checkpoint controls, otherwise referred to as restriction
points, which are regulated by a family of enzymes known as the
cyclin-dependent kinases (cdk).
[0004] In their turn, the cdks themselves are regulated at many
levels such as, for instance, binding to cyclins.
[0005] The coordinated activation and inactivation of different
cyclin/cdk complexes is necessary for normal progression through
the cell cycle. Both the critical G1-S and G2-M transitions are
controlled by the activation of different cyclin/cdk activities. In
G1, both cyclin D/cdk4 and cyclin E/cdk2 are thought to mediate the
onset of S-phase. Progression through S-phase requires the activity
of cyclin A/cdk2 whereas the activation of cyclin A/cdc2 (cdkl) and
cyclin B/cdc2 are required for the onset of metaphases.
[0006] For a general reference to cyclins and cyclin-dependent
kinases see, for instance, Kevin R. Webster et al. in Exp. Opin.
Invest. Drugs, 1998, Vol. 7(6), 865-887.
[0007] Checkpoint controls are defective in tumor cells due, in
part, to disregulation of cdk activity. For example, altered
expression of cyclin E and cdk's has been observed in tumor cells,
and deletion of the cdk inhibitor p27 KIP gene in mice has been
shown to result in a higher incidence of cancer.
[0008] Increasing evidence supports the idea that the cdks are
rate-limiting enzymes in cell cycle progression and, as such,
represent molecular targets for therapeutic intervention. In
particular, the direct inhibition of cdk/cyclin kinase activity
should be helpful in restricting the unregulated proliferation of a
tumor cell.
[0009] It has now been found that the 1H-pyrrolo{2,3-b]pyridine
derivatives of the invention are endowed with cdk/cyclin kinase
inhibitory activity and are thus useful in therapy as antitumor
agents whilst lacking, in terms of both toxicity and side effects,
the aforementioned drawbacks known for currently available
antitumor drugs.
[0010] More specifically, the compounds of this invention are
useful in the treatment of a variety of cancers including, but not
limited to: carcinoma such as bladder, breast, colon, kidney,
liver, lung, including small cell lung cancer, esophagus,
gall-bladder, ovary, pancreas, stomach, cervix, thyroid, prostate,
and skin, including squamous cell carcinoma; hematopoietic tumors
of lymphoid lineage, including leukemia, acute lymphocitic
leukemia, acute lymphoblastic leukemia, B-cell lymphoma,
T-cell-lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy
cell lymphoma and Burkett's lymphoma; hematopoietic tumors of
myeloid lineage, including acute and chronic myelogenous leukemias,
myelodysplastic syndrome and promyelocytic leukemia; tumors of
mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma;
tumors of the central and peripheral nervous system, including
astrocytoma, neuroblastoma, glioma and schwannomas; other tumors,
including melanoma, seminoma, teratocarcinoma, osteosarcoma,
xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer
and Kaposi's sarcoma.
[0011] Due to the key role of cdks in the regulation of cellular
proliferation, these azaindoles are also useful in the treatment of
a variety of cell proliferative disorders such as, for instance,
benign prostate hyperplasia, familial adenomatosis polyposis,
neuro-fibromatosis, psoriasis, vascular smooth cell proliferation
associated with atherosclerosis, pulmonary fibrosis, arthritis
glomerulonephritis and post-surgical stenosis and restenosis.
[0012] The compounds of the invention can be useful in the
treatment of Alzheimer's disease, as suggested by the fact that
cdk5 is involved in the phosphorylation of tau protein (J.
Biochem., 117, 741-749, 1995; FEBS Lett., 459, 421-426, 1999).
[0013] The compounds of this invention, as modulators of apoptosis,
could be useful in the treatment of cancer, viral infections,
prevention of AIDS development in HIV-infected individuals,
autoimmune diseases and neurodegenerative disorder.
[0014] The compounds of this invention could be useful in
inhibiting tumor angiogenesis and metastasis.
[0015] The compounds of this invention may also act as inhibitors
of other protein kinases, e.g. protein kinase C, her2, raf1, MEK1,
MAP kinase, EGF receptor, VEGF receptor, PDGF receptor, IGF
receptor, PI3 kinase, weel kinase, Src, Abl and thus be effective
in the treatment of diseases associated with other protein
kinases.
[0016] The compounds of the invention are also useful in the
treatment and/or prevention of chemotherapy-induced or
radiotherapy-induced alopecia.
[0017] Several 1H-pyrrolo[2,3-b]pyridines are known in the art as
therapeutic agents. Among them are some cyanoacrylamido derivatives
active as tyrosine kinase inhibitors as reported in WO 96/00226, in
the name of the applicant. Some other
acrylamido-1H-pyrrolo[2,3-b]pyridines are disclosed as antiallergic
agents, as reported in Chem. Pharm. Bull., 37(3), 684-7 (1989).
[0018] Accordingly, the present invention provides a method for
treating cell proliferative disorders associated with an altered
cell dependent kinase activity, by administering to a mammal in
need thereof an effective amount of a 1H-pyrrolo[2,3-b]pyridine
represented by formula (I): 2
[0019] wherein
[0020] R is a hydrogen or halogen atom or a group selected from
--CN, --OH, --OCOR.sub.4, --(CH.sub.2).sub.nNH.sub.2,
--(CH.sub.2).sub.nNHR.sub- .4, --(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4, or
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is either 0 or 1 ,
R.sub.4 and R.sub.5 are, independently from each other, hydrogen or
an optionally substituted group selected from alkyl, alkenyl,
alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkylalkynyl, heterocyclyl, heterocyclylalkyl,
heterocyclylalkenyl, heterocyclylalkynyl, aryl, arylalkyl,
arylalkenyl, arylalkynyl or, taken together to the nitrogen atom to
which they are bonded, form an optionally substituted heterocyclyl
group such as pyrrolidine, piperidine, piperazine and
morpholine;
[0021] R.sub.1 is hydrogen or an optionally substituted alkyl
group;
[0022] R.sub.2 is an optionally substituted group selected from
alkyl or aryl;
[0023] R.sub.3 is hydrogen or a group selected from
--CONR.sub.4R.sub.5, --COOR.sub.4, --CONHOR.sub.4,
--SO.sub.2NHR.sub.4, alkylsulphonylaminocarbonyl or perfluorinated
alkylsulphonylaminocarbonyl- ; wherein R.sub.4 and R.sub.5 have the
above reported meanings;
[0024] or a pharmaceutically acceptable salt thereof.
[0025] In a preferred embodiment of the method described above, the
cell proliferative disorder is selected from the group consisting
of cancer, Alzheimer's disease, viral infections, auto-immune
diseases and neurodegenerative disorders.
[0026] Specific types of cancer that may be treated include
carcinoma, hematopoietic tumors of lymphoid lineage, hematopoietic
tumors of myeloid lineage, tumors of mesenchymal origin, tumors of
the central and peripheral nervous system, melanoma, seminoma,
teratocarcinoma, osteosarcoma, xenoderoma pigmentosum,
keratoctanthoma, thyroid follicular cancer and Kaposi's
sarcoma.
[0027] In another preferred embodiment of the method described
above, the cell proliferative disorder is selected from benign
prostate hyperplasia, familial adenomatosis polyposis,
neuro-fibromatosis, psoriasis, vascular smooth cell proliferation
associated with atherosclerosis, pulmonary fibrosis, arthritis
glomerulonephritis and post-surgical stenosis and restenosis.
[0028] In addition, the inventive method provides tumor
angiogenesis and metastasis inhibition.
[0029] The compounds of this invention may also act as inhibitors
of other protein kinases, e.g. protein kinase C, her2, rafl, MEK1,
MAP kinase, EGF receptor, VEGF receptor, PDGF receptor, IGF
receptor, PI3 kinase, weel kinase, Src, Abl and thus be effective
in the treatment of diseases associated with other protein
kinases.
[0030] The present invention further provides a compound which is a
1H-pyrrolo{2,3-b]pyridine derivative represented by formula (I):
3
[0031] wherein
[0032] R is a hydrogen or halogen atom or a group selected from
--CN, --OH, --OCOR.sub.4, --(CH.sub.2).sub.nNH.sub.2,
--(CH.sub.2).sub.nNHR.sub- .4, --(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4, or
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is either 0 or 1,
R.sub.4 and R.sub.5 are, independently from each other, hydrogen or
an optionally substituted group selected from alkyl, alkenyl,
alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkylalkynyl, heterocyclyl, heterocyclylalkyl,
heterocyclylalkenyl, heterocyclylalkynyl, aryl, arylalkyl,
arylalkenyl, arylalkynyl or, taken together to the nitrogen atom to
which they are bonded, form an optionally substituted heterocyclyl
group such as pyrrolidine, piperidine, piperazine and
morpholine;
[0033] R.sub.1 is hydrogen or an optionally substituted alkyl
group;
[0034] R.sub.2 is an optionally substituted group selected from
alkyl or aryl;
[0035] R.sub.3 is hydrogen or a group selected from
--CONR.sub.4R.sub.5, --COOR.sub.4, --CONHOR.sub.4,
--SO.sub.2NHR.sub.4, alkylsulphonylaminocarbonyl or perfluorinated
alkylsulphonylaminocarbonyl- ; wherein R.sub.4 and R.sub.5 have the
above reported meanings;
[0036] or a pharmaceutically acceptable salt thereof.
[0037] In the present description, unless otherwise specified, with
the term halogen atom we intend a fluorine, chlorine, bromine or
iodine atom.
[0038] As used herein and unless otherwise indicated, alkyl stands
for straight or branched lower C.sub.1-C.sub.6 alkyl groups such
as, for instance, methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, and the like.
[0039] Unless otherwise specified, the terms alkenyl and alkynyl
refer to a straight or branched hydrocarbon chain radical with from
2 to 6 carbon atoms and at least one carbon to carbon double or
triple bond, respectively.
[0040] Unless otherwise specified, with the term cycloalkyl we
intend a C.sub.3-C.sub.6 cycloalkyl group such as, for instance,
cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl as well as a
bridged cycloalkyl group with from 6 to 10 carbon atoms such as
adamantane.
[0041] The term aryl stands for mono-, bi- or poly-carbocyclic or
heterocyclic hydrocarbons with from 1 to 4 ring moieties, either
fused or linked to each other by single bonds, wherein at least one
of the rings is aromatic.
[0042] The term heterocycle, hence encompassing heteroaromatic
rings also referred to as aryl, relates to a 5 or 6 membered
saturated or unsaturated carbocycle wherein one or more carbon
atoms are replaced by one or more atoms selected from nitrogen,
oxygen and sulphur.
[0043] Example of preferred aryl groups are, for instance, phenyl,
1-naphtyl, 2-naphthyl, indanyl, indenyl, biphenyl, benzocycloalkyl,
e.g. bicyclo[4.2.0]octa-1,3,5,-triene, benzodioxolyl, as well as
optionally benzocondensed pyrrolyl, furyl, thienyl, imidazolyl,
pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl,
pyrimidyl, tetrazolyl, thiadiazolyl, oxadiazolyl, triazolyl,
pyridazinyl and the like.
[0044] As noted above, each of the R.sub.1, R.sub.2, R.sub.4 and
R.sub.5 groups may be further substituted in any of the free
positions by one or more groups, for instance 1 to 6 groups,
selected from: halogen, nitro, oxo groups (.dbd.O), carboxy, cyano,
alkyl, perfluorinated alkyl, perfluorinated alkoxy, alkenyl,
alkynyl, cycloalkyl, aryl, heterocyclyl; amino groups and
derivatives thereof such as, for instance, alkylamino,
alkoxycarbonylalkylamino, dialkylamino, arylamino, diarylamino,
ureido, alkylureido or arylureido; carbonylamino groups and
derivatives thereof such as, for instance, hydrogenocarbonylamino
(HCONH--), alkylcarbonylamino, alkenylcarbonylamino,
arylcarbonylamino, alkoxycarbonylamino, aryloxycarbonylamino;
oxygen-substituted oximes such as, for instance,
alkoxycarbonylalkoxyimino or alkoxyimino; hydroxy groups and
derivatives thereof such as, for instance, alkoxy, aryloxy,
alkylcarbonyloxy, arylcarbonyloxy, alkylaminocarbonyloxy,
arylaminocarbonyloxy, cycloalkyloxy, cycloalkenyloxy; carbonyl
groups and derivatives thereof such as, for instance,
alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl,
cycloalkyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl,
dialkylaminocarbonyl; arylaminocarbonyl, sulfurated derivatives
such as, for instance, alkylthio, arylthio, alkylsulphonyl,
arylsulphonyl, alkylsulfamoyl, arylsulfamoyl, alkylsulphinyl,
arylsulphinyl, arylsulphonyloxy, aminosulfonyl,
alkylaminosulphonyl, dialkylaminosulphonyl or
arylaminosulphonyl.
[0045] In their turn, whenever appropriate, each of the above
possible substituents may be further substituted by one or more of
the aforementioned groups. Compounds of formula (I) wherein the
given R.sub.1, R.sub.2, R.sub.4 and R.sub.5, groups are substituted
by one or more of the aforementioned substituents which, in turn,
are optionally further substituted as set forth above, are given
below.
[0046] Just as an example, the compound
3-(6-{[(3-hydroxyphenyl)acetyl]ami-
no}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide is
represented by formula (I) wherein R.sub.1 is hydrogen; R.sub.2 is
aryl (e.g. phenyl); R.sub.3 is CONR.sub.4R.sub.5 wherein both
R.sub.4 and R.sub.5 are hydrogen atoms (e.g. CONH.sub.2); R is
--(CH.sub.2).sub.nNHCOR.sub.4 wherein n is 0 and R.sub.4 is an
alkyl group (e.g. methyl) wherein the alkyl is further substituted
by aryl (e.g. phenyl) which, in turn, is substituted by
hydroxy.
[0047] With the term perfluorinated alkyl and alkoxy group we
intend a C.sub.1-C.sub.6 alkyl or alkoxy group further substituted
by more than one fluorine atom such as, for instance,
trifluoromethyl, 2,2,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl,
trifluoromethoxy and the like.
[0048] Pharmaceutically acceptable salts of the compounds of
formula (I) are the acid addition salts with inorganic or organic,
e.g. nitric, hydrochloric, hydrobromic, sulphuric, perchloric,
phosphoric, acetic, trifluoroacetic, propionic, glycolic, lactic,
oxalic, malonic, malic, maleic, tartaric, citric, benzoic,
cinnamic, mandelic, methanesulphonic, isethionic and salicylic
acid, as well as the salts with inorganic or organic bases, e.g.
alkali or alkaline-earth metals, especially sodium, potassium,
calcium or magnesium hydroxides, carbonates or bicarbonates,
acyclic or cyclic amines, preferably methylamine, ethylamine,
diethylamine, triethylamine or piperidine.
[0049] The compounds of formula (I) may have asymmetric carbon
atoms and may therefore exist either as racemic admixtures or as
individual optical isomers.
[0050] Accordingly, the use as an antitumor agent of all the
possible isomers and their admixtures and of both the metabolites
and the pharmaceutically acceptable bio-precursors (otherwise
referred to as pro-drugs) of the compounds of formula (I) are also
within the scope of the present invention.
[0051] As above reported, within the compounds of formula (I)
wherein R is other than hydrogen, R itself may be in any of the
free positions of the pyridine ring, hence leading to 4-, 5- or
6-substituted 1H-pyrrolo[2,3-b]pyridine derivatives.
[0052] Preferred compounds of the invention are the compounds of
formula (I) wherein R is hydrogen, halogen, cyano, hydroxy or a
group --OCOR.sub.4, --(CH.sub.2).sub.nNH.sub.2,
--(CH.sub.2).sub.nNHR.sub.4, --(CH.sub.2).sub.nNHCOR.sub.4,
--(CH.sub.2).sub.nNHCONR.sub.4R.sub.5,
--(CH.sub.2).sub.nNHCOOR.sub.4,
--(CH.sub.2).sub.nNHSO.sub.2R.sub.4, wherein n is 0 or 1 and
R.sub.4 and R.sub.5 are, each independently, hydrogen or an
optionally substituted group selected from alkyl, heterocyclyl,
aryl or arylalkyl or, taken together to the nitrogen atom to which
they are bonded, R.sub.4 and R.sub.5 form an optionally substituted
pyrrolidino, piperidino, piperazino or morpholino group; and
R.sub.1, R.sub.2 and R.sub.3 have the above reported meanings.
[0053] Still more preferred, within this latter class, are the
compounds of formula (I) wherein R.sub.3 is hydrogen or a group
selected from --CONR.sub.4R.sub.5, --COOR.sub.4 or --CONHOR.sub.4
wherein R.sub.4 is as above defined.
[0054] Examples of preferred compounds of the invention, whenever
appropriate in the form of pharmaceutically acceptable salts, e.g.
hydrobromide or hydrochloride salts, are the following:
[0055] 1.
3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide-
;
[0056] 2.
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-prope-
namide;
[0057] 3.
3-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamid-
e;
[0058] 4.
3-(6-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide-
;
[0059] 5.
3-(6-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide-
;
[0060] 6.
3-(6-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenami-
de;
[0061] 7.
3-[6-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penamide;
[0062] 8.
3-{6-[(methylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenamide;
[0063] 9.
3-{6-[(benzylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenamide;
[0064] 10.
N-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-6-yl}methyl)benzamide;
[0065] 11.
2-phenyl-3-(6-{[(phenylacetyl)amino]methyl}-1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenamide;
[0066] 12.
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin--
6-yl benzoate;
[0067] 13.
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin--
6-yl acetate;
[0068] 14.
3-[6-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0069] 15.
3-[6-(ethylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penamide;
[0070] 16.
3-[6-(isopropylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
-propenamide;
[0071] 17.
3-[6-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenamide;
[0072] 18.
3-(6-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenam-
ide;
[0073] 19.
3-[6-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
-propenamide;
[0074] 20.
3-[6-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-
-2-propenamide;
[0075] 21.
3-{6-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenamide;
[0076] 22.
4-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-6-yl}amino)benzamide;
[0077] 23.
3-[6-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenam-
ide;
[0078] 24.
2-phenyl-3-[6-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-
-2-propenamide;
[0079] 25.
2-phenyl-3-[6-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin--
3-yl]-2-propenamide;
[0080] 26.
3-[6-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0081] 27.
3-(6-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenamide;
[0082] 28.
3-[6-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0083] 29.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}benzamide;
[0084] 30.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-4-bromobenzamide;
[0085] 31.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-3-hydroxybenzamide;
[0086] 32.
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-
-b]pyridin-6-yl}benzamide;
[0087] 33.
3-[6-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide;
[0088] 34.
2-phenyl-3-{6-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl}-2-propenamide;
[0089] 35.
3-(6-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenamide;
[0090] 36.
3-(6-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide;
[0091] 37.
3-(6-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-phenyl-2-propenamide;
[0092] 38.
2-phenyl-3-{6-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyrid-
in-3-yl}-2-propenamide;
[0093] 39.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-1H-indole-3-carboxamide;
[0094] 40.
3-{6-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-phenyl-2-propenamide;
[0095] 41.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-2-thiophenecarboxamide;
[0096] 42.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}[1,1'-biphenyl]-4-carboxamide;
[0097] 43.
3-{6-[([1,1'-biphenyl]-4-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyrid-
in-3-yl}-2-phenyl-2-propenamide;
[0098] 44.
3-{6-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl}-2-phenyl-2-propenamide;
[0099] 45.
2-phenyl-3-{6-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]-
pyridin-3-yl}-2-propenamide;
[0100] 46.
3-{6-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenamide;
[0101] 47.
3-(6-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-phenyl-2-propenamide;
[0102] 48.
3-{6-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;
[0103] 49.
3-(6-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenamide;
[0104] 50.
3-(6-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenamide;
[0105] 51.
3-(6-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-phenyl-2-propenamide;
[0106] 52.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-1-piperidinecarboxamide;
[0107] 53.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-4-methyl-1-piperazinecarboxamide;
[0108] 54.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-4-morpholinecarboxamide;
[0109] 55.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-6-yl}-1-pyrrolidinecarboxamide;
[0110] 56. ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]py-
ridin-6-ylcarbamate;
[0111] 57. tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-
-b]pyridin-6-ylcarbamate;
[0112] 58.
3-{6-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-p-
henyl-2-propenamide;
[0113] 59.
2-phenyl-3-{6-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin--
3-yl}-2-propenamide;
[0114] 60.
2-phenyl-3-(6-{[(phenylsulfonyl)methyl]amino}-1H-pyrrolo[2,3-b]-
pyridin-3-yl)-2-propenamide;
[0115] 61.
3-(6-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2-
,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0116] 62.
3-{6-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyr-
idin-3-yl}-2-phenyl-2-propenamide;
[0117] 63.
3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenami-
de;
[0118] 64.
3-(4-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenam-
ide;
[0119] 65.
3-[4-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
-propenamide;
[0120] 66.
3-[4-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-
-2-propenamide;
[0121] 67.
3-{4-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenamide;
[0122] 68.
4-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}amino)benzamide;
[0123] 69.
3-[4-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
-propenamide;
[0124] 70.
2-phenyl-3-[4-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-
-2-propenamide;
[0125] 71.
2-phenyl-3-[4-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin--
3-yl]-2-propenamide;
[0126] 72.
3-(4-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamid-
e;
[0127] 73.
3-[4-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0128] 74.
3-[4-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenamide;
[0129] 75.
3-[4-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0130] 76.
3-(4-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenamide;
[0131] 77.
3-[4-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0132] 78.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-4-yl}benzamide;
[0133] 79.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-4-yl}-4-bromobenzamide;
[0134] 80.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-4-yl}-3-hydroxybenzamide;
[0135] 81.
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,
3-b]pyridin-4-yl}benzamide;
[0136] 82.
3-[4-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide;
[0137] 83.
2-phenyl-3-{4-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl} -2-propenamide;
[0138] 84.
3-(4-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl) -2-phenyl-2-propenamide;
[0139] 85.
3-(4-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl) -2-phenyl-2-propenamide;
[0140] 86.
3-(4-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3--
yl) -2-phenyl-2-propenamide;
[0141] 87. 2-phenyl-3-{4-[(3-pyridinylacetyl)amino]-1H-pyrrolo
[2,3-b]pyridin-3-yl}-2-propenamide;
[0142] 88. N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,
3-b]pyridin-4-yl}-1H-indole-3-carboxamide;
[0143] 89.
3-{4-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-phenyl-2-propenamide;
[0144] 90.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-4-yl}-2-thiophenecarboxamide;
[0145] 91.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyrid-
in-4-yl}[1,1'-biphenyl]-4-carboxamide;
[0146] 92.
3-{4-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3--
yl}-2-phenyl-2-propenamide;
[0147] 93.
2-phenyl-3-{4-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]-
pyridin-3-yl}-2-propenamide;
[0148] 94.
3-{4-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl
}-2-phenyl-2-propenamide;
[0149] 95.
3-(4-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-phenyl-2-propenamide;
[0150] 96.
3-{4-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;
[0151] 97.
3-(4-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenamide;
[0152] 98.
3-(4-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-phenyl-2-propenamide;
[0153] 99.
3-(4-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-phenyl-2-propenamide;
[0154] 100.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}-1-piperidinecarboxamide;
[0155] 101.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}-1-pyrrolidinecarboxamide;
[0156] 102.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}-4-methyl-1-piperazinecarboxamide;
[0157] 103.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}-4-morpholinecarboxamide;
[0158] 104. 1-ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b-
]pyridin-4-ylcarbamate;
[0159] 105. 1-tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[-
2,3-b]pyridin-4-ylcarbamate;
[0160] 106.
3-{4-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;
[0161] 107.
2-phenyl-3-{4-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-propenamide;
[0162] 108.
3-{4-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;
[0163] 109.
3-{4-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenamide;
[0164] 110.
3-(4-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0165] 111.
3-(5-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenami-
de;
[0166] 112.
3-[5-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide;
[0167] 113.
3-[5-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-
-2-propenamide;
[0168] 114.
3-[5-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide;
[0169] 115.
3-(5-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenamide;
[0170] 116.
3-[5-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide;
[0171] 117.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}benzamide;
[0172] 118.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-4-bromobenzamide;
[0173] 119.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-3-hydroxybenzamide;
[0174] 120.
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,-
3-b]pyridin-5-yl}benzamide;
[0175] 121.
3-[5-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenamide;
[0176] 122.
2-phenyl-3-{5-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenamide;
[0177] 123.
3-(5-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenamide;
[0178] 124.
3-(5-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenamide;
[0179] 125.
3-(5-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide;
[0180] 126.
2-phenyl-3-{5-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenamide;
[0181] 127.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-1H-indole-3-carboxamide;
[0182] 128.
3-{5-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenamide;
[0183] 129.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-2-thiophenecarboxamide;
[0184] 130.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}[1,1'-biphenyl]-4-carboxamide;
[0185] 131.
3-{5-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenamide;
[0186] 132.
2-phenyl-3-{5-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenamide;
[0187] 133.
3-{5-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-p-
henyl-2-propenamide;
[0188] 134.
3-(5-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide;
[0189] 135.
3-{5-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenamide;
[0190] 136.
3-(5-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-phenyl-2-propenamide;
[0191] 137.
3-(5-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-phenyl-2-propenamide;
[0192] 138.
3-(5-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide;
[0193] 139.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-1-piperidinecarboxamide;
[0194] 140.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-1-pyrrolidinecarboxamide;
[0195] 141.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-4-methyl-1-piperazinecarboxamide;
[0196] 142.
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-5-yl}-4-morpholinecarboxamide;
[0197] 143. ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]p-
yridin-5-ylcarbamate;
[0198] 144. tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,-
3-b]pyridin-5-ylcarbamate;
[0199] 145.
3-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;;
[0200] 146.
2-phenyl-3-{5-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-propenamide;
[0201] 147.
3-{5-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;
[0202] 148.
3-{5-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenamide;
[0203] 149.
3-(5-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0204] 150.
3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0205] 151.
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-pro-
penoic acid;
[0206] 152.
3-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoi- c
acid;
[0207] 153.
3-(6-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0208] 154.
3-(6-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0209] 155.
3-(6-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propeno- ic
acid;
[0210] 156.
3-[6-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0211] 157.
3-{6-[(methylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenoic acid;
[0212] 158.
3-{6-[(benzylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenoic acid;
[0213] 159.
3-{6-[(benzoylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-p-
henyl-2-propenoic acid;
[0214] 160.
2-phenyl-3-(6-{[(phenylacetyl)amino]methyl}-1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenoic acid;
[0215] 161.
3-[6-(benzoyloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openoic acid;
[0216] 162.
3-[6-(acetyloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penoic acid;
[0217] 163.
3-[6-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0218] 164.
3-[6-(ethylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openoic acid;
[0219] 165.
3-[6-(isopropylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenoic acid;
[0220] 166.
3-[6-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl- -2-
propenoic acid;
[0221] 167.
3-(6-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propeno- ic
acid;
[0222] 168.
3-[6-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-- 2-
propenoic acid;
[0223] 169.
3-[6-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-pheny-
l-2- propenoic acid;
[0224] 170.
3-{6-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-
-2-phenyl-2-propenoic acid;
[0225] 171.
3-{6-[4-(aminocarbonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-
-2-phenyl-2-propenoic acid;
[0226] 172.
3-[6-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propeno- ic
acid;
[0227] 173.
2-phenyl-3-[6-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl-
]-2- propenoic acid;
[0228] 174.
2-phenyl-3-[6-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin-
-3-yl]-2-propenoic acid;
[0229] 175.
3-[6-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0230] 176.
3-(6-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid;
[0231] 177.
3-[6-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0232] 178.
3-[6-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid;
[0233] 179.
3-{6-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0234] 180.
3-{6-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0235] 181.
3-{6-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0236] 182.
3-[6-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid;
[0237] 183.
2-phenyl-3-{6-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0238] 184.
3-(6-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid;
[0239] 185.
3-(6-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenoic acid;
[0240] 186.
3-(6-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0241] 187.
2-phenyl-3-{6-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0242] 188.
3-{6-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0243] 189.
3-{6-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenoic acid;
[0244] 190.
2-phenyl-3-{6-[(2-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0245] 191.
3-{6-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0246] 192.
3-{6-[([1,1'-biphenyl]-4-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-phenyl-2-propenoic acid;
[0247] 193.
3-{6-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0248] 194.
2-phenyl-3-{6-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenoic acid;
[0249] 195.
3-{6-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-p-
henyl-2-propenoic acid;
[0250] 196.
3-(6-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0251] 197.
3-{6-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenoic acid;
[0252] 198.
3-(6-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-phenyl-2-propenoic acid;
[0253] 199.
3-(6-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-phenyl-2-propenoic acid;
[0254] 200.
3-(6-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0255] 201.
2-phenyl-3-{6-[(1-piperidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]-
pyridin-3-yl}-2-propenoic acid;
[0256] 202.
2-phenyl-3-{6-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenoic acid;
[0257] 203.
3-(6-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0258] 204.
3-{6-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0259] 205.
3-{6-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0260] 206.
3-{6-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenoic acid;
[0261] 207.
3-{6-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0262] 208.
2-phenyl-3-{6-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-propenoic acid;
[0263] 209.
2-phenyl-3-(6-{[(phenylsulfonyl)methyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-propenoic acid;
[0264] 210.
3-(6-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0265] 211.
3-{6-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0266] 212.
3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoi- c
acid;
[0267] 213.
3-(4-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propeno- ic
acid;
[0268] 214.
3-[4-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenoic acid;
[0269] 215.
3-[4-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-pheny-
l-2-propenoic acid;
[0270] 216.
3-{4-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-
-2-phenyl-2-propenoic acid;
[0271] 217.
3-{4-[4-(aminocarbonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-
-2-phenyl-2-propenoic acid;
[0272] 218.
3-[4-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--
2-propenoic acid;
[0273] 219.
2-phenyl-3-[4-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl-
]-2-propenoic acid;
[0274] 220.
2-phenyl-3-[4-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin-
-3-yl]-2-propenoic acid;
[0275] 221.
3-(4-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0276] 222.
3-[4-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--2--
propenoic acid;
[0277] 223.
3-[4-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-
-2-propenoic acid;
[0278] 224.
3-[4-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--2--
propenoic acid;
[0279] 225.
3-(4-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid;
[0280] 226.
3-[4-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl--2--
propenoic acid;
[0281] 227.
3-[4-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid;
[0282] 228.
3-{4-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0283] 229.
3-{4-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0284] 230.
3-{4-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0285] 231.
3-[4-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid;
[0286] 232.
2-phenyl-3-{4-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0287] 233.
3-(4-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid;
[0288] 234.
3-(4-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenoic acid;
[0289] 235.
3-(4-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0290] 236.
2-phenyl-3-{4-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0291] 237.
3-{4-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0292] 238.
3-{4-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenoic acid;
[0293] 239.
2-phenyl-3-{4-[(3-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0294] 240.
3-{4-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0295] 241.
3-{4-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0296] 242.
2-phenyl-3-{4-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenoic acid;
[0297] 243.
3-{4-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-p-
henyl-2-propenoic acid;
[0298] 244.
3-(4-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0299] 245.
3-{4-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenoic acid;
[0300] 246.
3-(4-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-phenyl-2-propenoic acid;
[0301] 247.
3-(4-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-phenyl-2-propenoic acid;
[0302] 248.
3-(4-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0303] 249.
2-phenyl-3-{4-[(1-piperidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]-
pyridin-3-yl}-2-propenoic acid;
[0304] 250.
2-phenyl-3-{4-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenoic acid;
[0305] 251.
3-(4-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0306] 252.
3-{4-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0307] 253.
3-{4-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0308] 254.
3-{4-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenoic acid;
[0309] 255.
3-{4-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0310] 256.
2-phenyl-3-{4-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-propenoic acid;
[0311] 257.
3-{4-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0312] 258.
3-{4-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0313] 259.
3-(4-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0314] 260.
3-(5-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0315] 261.
3-[5-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0316] 262.
3-[5-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-
-2-propenoic acid;
[0317] 263.
3-[5-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0318] 264.
3-(5-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid;
[0319] 265.
3-[5-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0320] 266.
3-[5-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid;
[0321] 267.
3-{5-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0322] 268.
3-{5-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0323] 269.
3-{5-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0324] 270.
3-[5-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2--
propenoic acid;
[0325] 271.
2-phenyl-3-{5-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0326] 272.
3-(5-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-phenyl-2-propenoic acid;
[0327] 273.
3-(5-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-phenyl-2-propenoic acid;
[0328] 274.
3-(5-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0329] 275.
2-phenyl-3-{5-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0330] 276.
3-{5-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0331] 277.
3-{5-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenoic acid;
[0332] 278.
2-phenyl-3-{5-[(3-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0333] 279.
3-{5-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0334] 280.
3-{5-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0335] 281.
2-phenyl-3-{5-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenoic acid;
[0336] 282.
3-{5-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-p-
henyl-2-propenoic acid;
[0337] 283.
3-(5-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0338] 284.
3-{5-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-
-phenyl-2-propenoic acid;
[0339] 285.
3-(5-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-phenyl-2-propenoic acid;
[0340] 286.
3-(5-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-phenyl-2-propenoic acid;
[0341] 287.
3-(5-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0342] 288.
2-phenyl-3-{5-[(1-piperidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]-
pyridin-3-yl}-2-propenoic acid;
[0343] 289.
2-phenyl-3-{5-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b-
]pyridin-3-yl}-2-propenoic acid;
[0344] 290.
3-(5-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0345] 291.
3-{5-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0346] 292.
3-{5-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0347] 293.
3-{5-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-y-
l}-2-phenyl-2-propenoic acid;
[0348] 294.
3-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0349] 295.
2-phenyl-3-{5-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-propenoic acid;
[0350] 296.
3-{5-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0351] 297.
3-{5-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0352] 298.
3-(5-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[-
2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0353] 299.
2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
[0354] 300. 2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid;
[0355] 301.
N-butyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenami-
de;
[0356] 302.
2-(4-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0357] 303.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(4-tolyl)-2-propenoic acid;
[0358] 304.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[2-(trifluoromethyl)phenyl-
]-2-propenoic acid;
[0359] 305.
2-(1-acetyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenoic acid;
[0360] 306.
2-(1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi- c
acid;
[0361] 307.
2-(3-fluoro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid;
[0362] 308.
2-(2,3-dihydro-1H-inden-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenoic acid;
[0363] 309.
2-(3-pyridinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid;
[0364] 310.
2-(4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen- oic
acid;
[0365] 311.
2-(4-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen- oic
acid;
[0366] 312.
2-(2-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen- oic
acid;
[0367] 313.
2-(2-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen- oic
acid;
[0368] 314.
2-[1,1'-biphenyl]-4-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0369] 315.
2-(4-hydroxy-5-isopropyl-2-methylphenyl)-3-(1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenoic acid;
[0370] 316.
2-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenoic acid;
[0371] 317.
2-(3-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0372] 318.
2-(3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen- oic
acid;
[0373] 319.
2-(3-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi- c
acid;
[0374] 320.
2-(1,3-benzodioxol-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenoic acid;
[0375] 321.
2-(3,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid;
[0376] 322.
2-(3-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0377] 323.
2-(4-butoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0378] 324.
2-(3-chloro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid;
[0379] 325.
2-[4-(methylsulfonyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid;
[0380] 326.
2-(4-ethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0381] 327.
2-(3-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0382] 328.
2-(2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0383] 329.
2-(3,4-dihydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid;
[0384] 330.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(2-thienyl)-2-propenoic
acid;
[0385] 331.
2-(2-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi- c
acid;
[0386] 332.
2-(2-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0387] 333.
2-(2-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0388] 334.
2-(2,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0389] 335.
2-(2-chloro-6-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenoic acid;
[0390] 336.
2-(2,6-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0391] 337.
2-(2,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid;
[0392] 338.
2-(3,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0393] 339.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3,4,5-trimethoxyphenyl)-2-
-propenoic acid;
[0394] 340.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[3-(trifluoromethyl)phenyl-
]-2-propenoic acid;
[0395] 341.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethyl)phenyl-
]-2-propenoic acid;
[0396] 342.
2-[3,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenoic acid;
[0397] 343.
2-(2,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0398] 344.
2-(2,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0399] 345.
.sup.2-(3,.sup.4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-propenoic acid;
[0400] 346.
2-(3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid;
[0401] 347.
2-[4-(benzyloxy)-3-methoxyphenyl]-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenoic acid;
[0402] 348.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3-thienyl)-2-propenoic
acid;
[0403] 349.
2-(5-methoxy-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenoic acid;
[0404] 350.
2-(1-naphthyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid;
[0405] 351.
2-(3-methyl-1-benzothien-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-propenoic acid;
[0406] 352.
2-(3,4-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid;
[0407] 353.
2-(4-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi- c
acid;
[0408] 354.
2-[4-(acetylamino)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenoic acid;
[0409] 355.
2-[4-amino-phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0410] 356.
2-(5-bromo-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenoic acid;
[0411] 357.
2-(1-methyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenoic acid;
[0412] 358.
2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno- ic
acid;
[0413] 359.
2-[2,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenoic acid;
[0414] 360.
2-(2,3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenoic acid;
[0415] 361.
2-[5-(benzyloxy)-1H-indol-3-yl]-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenoic acid;
[0416] 362.
2-(2-amino-1,3-thiazol-4-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid;
[0417] 363. 2-mesityl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid;
[0418] 364.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethoxy)pheny-
l]-2-propenoic acid;
[0419] 365.
2-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenoic acid;
[0420] 366.
2-[4-(2-amino-2-oxoethoxy)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenoic acid;
[0421] 367.
2-{4-[2-oxo-2-(1-pyrrolidinyl)ethoxy]phenyl}-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenoic acid;
[0422] 368.
2-(3-hydroxy-5-methoxy-2-propylphenyl)-3-(1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-propenoic acid;
[0423] 369.
2-(4-phenoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen- oic
acid;
[0424] 370.
2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenoic acid;
[0425] 371.
2-{3-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenoic acid;
[0426] 372.
2-{4-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenoic acid;
[0427] 373.
2-[4-(1-pyrrolidinyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid;
[0428] 374.
2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenoic acid;
[0429] 375.
2-(4-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0430] 376.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(4-tolyl)-2-propenamide;
[0431] 377.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[2-(trifluoromethyl)phenyl-
]-2-propenamide;
[0432] 378.
2-(1-acetyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenamide;
[0433] 379.
2-(1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide;
[0434] 380.
2-(3-fluoro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0435] 381.
2-(2,3-dihydro-1H-inden-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenamide;
[0436] 382.
2-(3-pyridinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamid-
e;
[0437] 383.
2-(4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0438] 384.
2-(4-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0439] 385.
2-(2-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0440] 386.
2-(2-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0441] 387.
2-[1,1'-biphenyl]-4-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0442] 388.
2-(4-hydroxy-5-isopropyl-2-methylphenyl)-3-(1H-pyrrolo[2,3-b]p-
yridin-3-yl)-2-propenamide;
[0443] 389.
2-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenamide;
[0444] 390.
2-(3-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0445] 391.
2-(3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0446] 392.
2-(3-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide;
[0447] 393.
2-(1,3-benzodioxol-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenamide;
[0448] 394.
2-(3,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide;
[0449] 395.
2-(3-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0450] 396.
2-(4-butoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0451] 397.
2-(3-chloro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0452] 398.
2-[4-(methylsulfonyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0453] 399.
2-(4-ethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0454] 400.
2-(3-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0455] 401.
2-(2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0456] 402.
2-(3,4-dihydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide;
[0457] 403.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(2-thienyl)-2-propenamide;
[0458] 404.
2-(2-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide;
[0459] 405.
2-(2-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0460] 406.
2-(2-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0461] 407.
2-(2,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0462] 408.
2-(2-chloro-6-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenamide;
[0463] 409.
2-(2,6-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0464] 410.
2-(2,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide;
[0465] 411.
2-(3,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0466] 412.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3,4,5-trimethoxyphenyl)-2-
-propenamide;
[0467] 413.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[3-(trifluoromethyl)phenyl-
]-2-propenamide;
[0468] 414.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethyl)phenyl-
]-2-propenamide;
[0469] 415.
2-[3,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenamide;
[0470] 416.
.sup.2-(2,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenamide;
[0471] 417.
2-(2,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0472] 418.
2-(3,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0473] 419.
2-(3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide;
[0474] 420.
2-[4-(benzyloxy)-3-methoxyphenyl]-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenamide;
[0475] 421.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3-thienyl)-2-propenamide;
[0476] 422.
2-(5-methoxy-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenamide;
[0477] 423.
2-(1-naphthyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide-
;
[0478] 424.
2-(3-methyl-1-benzothien-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-propenamide;
[0479] 425.
2-(3,4-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide;
[0480] 426.
2-(4-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide;
[0481] 427.
2-[4-(acetylamino)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenamide;
[0482] 428.
2-[4-amino-phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0483] 429.
2-(5-bromo-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenamide;
[0484] 430.
2-(1-methyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenamide;
[0485] 431.
2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide;
[0486] 432.
2-[2,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenamide;
[0487] 433.
2-(2,3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenamide;
[0488] 434.
2-[5-(benzyloxy)-1H-indol-3-yl]-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenamide;
[0489] 435.
2-(2-amino-1,3-thiazol-4-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0490] 436.
2-mesityl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
[0491] 437.
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethoxy)pheny-
l]-2-propenamide;
[0492] 438.
2-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenamide;
[0493] 439.
2-[4-(2-amino-2-oxoethoxy)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenamide;
[0494] 440.
2-{4-[2-oxo-2-(1-pyrrolidinyl)ethoxy]phenyl}-3-(1H-pyrrolo[2,3-
-b]pyridin-3-yl)-2-propenamide;
[0495] 441.
2-(3-hydroxy-5-methoxy-2-propylphenyl)-3-(1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-propenamide;
[0496] 442.
2-(4-phenoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0497] 443.
2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenamide;
[0498] 444.
2-{3-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide;
[0499] 445.
2-{4-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide;
[0500] 446.
2-[4-(1-pyrrolidinyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0501] 447.
2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenamide;
[0502] 448.
N-benzyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide;
[0503] 449.
N-(4-methoxyphenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0504] 450.
1-(4-morpholinyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propen-1-one
[0505] 451.
N-(4-chlorophenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenamide;
[0506] 452.
N,N-dimethyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enamide;
[0507] 453.
N-isopropyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope-
namide;
[0508] 454.
2-phenyl-1-(1-piperidinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propen-1-one
[0509] 455.
N-[(3-aminomethyl)-pyridin]-2-phenyl-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenamide;
[0510] 456.
N-benzyl-N-methyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenamide;
[0511] 457.
N-(1H-indazol-6-yl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0512] 458.
N-(4-methoxybenzyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0513] 459.
N-(4-chlorobenzyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenamide;
[0514] 460.
N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-phenyl-3-(1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-propenamide;
[0515] 461.
N-furfuryl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide;
[0516] 462.
N-(4-hydroxypiperidin)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenamide;
[0517] 463.
N-(3-hydroxypiperidin)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenamide;
[0518] 464.
N-(3-methoxyphenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide;
[0519] 465.
N,2-diphenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
[0520] 466.
3-[3-(4-methyl-1-piperazinyl)-3-oxo-2-phenyl-1-propenyl]-1H-py-
rrolo[2,3-b]pyridine
[0521] 467.
N-[4-(dimethylamino)phenyl]-2-phenyl-3-(1H-pyrrolo[2,3-b]pyrid-
in-3-yl)-2-propenamide;
[0522] 468.
N-(3-chlorophenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-propenamide;
[0523] 469.
N,N-diethyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope-
namide;
[0524] 470.
3-[3-(4-benzyl-1-piperazinyl)-3-oxo-2-phenyl-1-propenyl]-1H-py-
rrolo[2,3-b]pyridine
[0525] 471.
2-[2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoyl]-1,2-
,3,4-tetrahydroisoquinoline
[0526] 472.
N-(tert-butoxy)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenamide;
[0527] 473. N-hydroxy-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)
2-propenamide;
[0528] 474.
N-methyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide;
[0529] 475.
3-{6-[(2-naphthylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenamide;
[0530] 476.
2-(3-chloro-4-hydroxyphenyl)-3-{6-[(2-naphthylacetyl)amino]-1H-
-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide;
[0531] 477.
3-{6-[(1-naphthylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenamide;
[0532] 478.
2-(3-chloro-4-hydroxyphenyl)-3-{6-[(1-naphthylacetyl)amino]-1H-
-pyrrolo[2,3-b]pyridin-3-yl}-2-propenamide;
[0533] 479.
2-phenyl-3-[6-({[4-(2-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[-
2,3-b]pyridin-3-yl]-2-propenamide;
[0534] 480.
2-(3-chloro-4-hydroxyphenyl)-3-[6-({[4-(2-thienyl)phenyl]acety-
l}amino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamide;
[0535] 481.
2-phenyl-3-[6-({[4-(3-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[-
2,3-b]pyridin-3-yl]-2-propenamide;
[0536] 482.
2-(3-chloro-4-hydroxyphenyl)-3-[6-({[4-(3-thienyl)phenyl]acety-
l}amino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamide;
[0537] 483.
3-(6-{[(3',4'-difluoro[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-py-
rrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0538] 484.
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(3',4'-difluoro[1,1'-biphe-
nyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
[0539] 485.
3-(6-{[(5'-fluoro-2'-methoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-
-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0540] 486.
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(5'-fluoro-2'-methoxy[1,1'-
-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide-
;
[0541] 487.
3-(6-{[(2',5'-difluoro[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-py-
rrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0542] 488.
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(2',5'-difluoro[1,1'-biphe-
nyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide;
[0543] 489.
3-(6-{[(3'-ethoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo-
[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0544] 490.
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(3'-ethoxy[1,1'-biphenyl]--
4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide.
[0545] Another object of the present invention is a process for
preparing the compounds of formula (I) which is carried out
according to methods well known to the person skilled in the art,
for instance by applying known reactions to suitable intermediate
substrates.
[0546] In particular, the compounds of formula (I) object of the
present invention can be obtained, for instance, by a process
comprising reacting a compound of formula (II) 4
[0547] wherein R and R.sub.1 are as above indicated, with a
compound of formula (III) 5
[0548] wherein R.sub.2 is as above indicated and X represents a
hydrogen atom, a --COOH carboxy group or a derivative thereof such
as --COOR.sub.4 or --CONR.sub.4R.sub.5, wherein R.sub.4 and R.sub.5
are as above indicated, thus obtaining a compound of formula (I)
wherein R, R.sub.1 and R.sub.2 are as defined above and R.sub.3 is
a hydrogen atom, a --COOH carboxy group or a derivative thereof
such as --COOR.sub.4 or --CONR.sub.4R.sub.5, wherein R.sub.4 and
R.sub.5 are as above indicated; and, if desired, converting the
said compound of formula (I) into another compound of formula (I)
and/or into a salt thereof.
[0549] The above process is an analogy process which can be carried
out according to well known methods.
[0550] As an example, the preparation of a compound of formula (I)
wherein R.sub.3 is a COOH carboxy group, according to the process
object of the invention, is carried out according to conventional
techniques by reacting the above compound of formula (II) with an
arylacetic acid derivative of formula (III) wherein X is hydrogen,
for instance in acetic anhydride in the presence of a suitable base
such as triethylamine, pyridine or diisopropylethylamine, at a
temperature ranging from about 60.degree. C. to 140.degree. C. for
a suitable time, i.e. from about 1 hour to several hours.
[0551] The preparation of a compound of formula (I) wherein R.sub.3
is hydrogen, according to the process object of the invention, is
carried out according to conventional techniques by reacting the
above compound of formula (II) with a malonic acid derivative of
formula (III) wherein X is a --COOH carboxy group, in the presence
of a suitable base such as pyridine, piperidine or mixtures
thereof, at a temperature ranging from about 60.degree. C. to about
140.degree. C. and for a suitable time varying from about 3 hours
to several hours.
[0552] Likewise, the preparation of a compound of formula (I)
wherein R.sub.3 is a carboxy derivative other than COOH, such as
--CONR.sub.4R.sub.5 or --COOR.sub.4, is carried out according to
conventional techniques by reacting a compound of formula (II) with
a derivative of formula (III) wherein X is --CONR.sub.4R.sub.5 or
--COOR.sub.4.
[0553] Also the optional conversion of a compound of formula (I)
into another compound of formula (I) can be carried out according
to known methods.
[0554] As an example, compounds of formula (I) wherein R.sub.3 is a
group --CONR.sub.4R.sub.5 can be also obtained from the
corresponding compounds of formula (I) wherein R.sub.3 is COOH, by
reaction with a compound of formula
R.sub.4--NH--R.sub.5 (IV)
[0555] wherein R.sub.4 and R.sub.5 are as defined above.
[0556] The reaction between a compound of formula (IV) and a
carboxylic acid of formula (I) can be carried out in the presence
of a coupling agent such as, for instance, carbodiimide, i.e.
1,3-dicyclohexylcarbodiim- ide, 1,3-diisopropylcarbodiimide,
O-(benzotriazol-1-yl)-N,N,N',N'-tetramet- hyluronium
tetrafluoborate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide,
N-cyclohexylcarbodiimide-N'-propyloxymethyl polystyrene or
N-cyclohexylcarbodiimide-N'-methyl polystyrene, in a suitable
solvent such as, for instance, dichloromethane, chloroform,
tetrahydrofuran, diethyl ether, 1,4-dioxane, acetonitrile, toluene,
or N,N-dimethylformamide at a temperature ranging from about
-20.degree. C. to reflux for a suitable time, i.e. from about 30
min. to about 96 hours, optionally in the presence of a suitable
catalyst such as 4-dimethylaminopyridine or in the presence of a
further coupling reagent such as N-hydroxybenzotriazole.
[0557] N-hydroxybenzotriazole ammonium salt can be conveniently
used as a reactant in the preparation of the compounds of formula
(I) as above indicated wherein R.sub.3 is --CONR.sub.4R.sub.5,
R.sub.4 and R.sub.5 being both hydrogen atoms.
[0558] The reaction between a compound of formula (IV) and a
carboxylic acid of formula (I) can be also carried out, for
example, by a mixed anhydride method, using an alkyl chloroformate,
such as ethyl, iso-butyl, or iso-propyl chloroformate, in the
presence of a tertiary base, such as triethylamine,
N,N-diisopropylethylamine or pyridine, in a suitable solvent such
as, for instance, toluene, dichloromethane, chloroform,
tetrahydrofuran, acetonitrile, diethyl ether, 1,4-dioxane, or
N,N-dimethylformamide, at a temperature ranging from about
-30.degree. C. to room temperature.
[0559] Compounds of formula (I) wherein R.sub.3 is a --COOR.sub.4
group can be obtained from the corresponding compounds of formula
(I) wherein R.sub.3 is COOH by reaction with a compound of
formula
R.sub.4--OH (V)
[0560] wherein R.sub.4 is as defined above.
[0561] The reaction between a compound of formula (V) and a
carboxylic acid of formula (I) is an is an analogy process which
can be carried out according to well known methods.
[0562] Compounds of formula (I) wherein R.sub.3 is --COOR.sub.4
can, in turn, be converted into compounds of formula (I) wherein
R.sub.3 is --CONR.sub.4R.sub.5 by reaction with a compound of
formula (IV) in a suitable solvent such as 1,4-dioxane,
tetrahydrofuran, N,N'-dimethylformamide at a temperature ranging
from about 20.degree. C. to 80.degree. C. for a suitable time, i.e.
from about 10 hour to about 96 hours.
[0563] Compounds of formula (I) wherein R.sub.3 is --CONHOR.sub.4
can be obtained from the corresponding compounds of formula (I)
wherein R.sub.3 is COOH by reaction with a compound of formula
NH.sub.2--OR.sub.4 (VI)
[0564] wherein R.sub.4 is as defined above.
[0565] The reaction between a compound of formula (VI) and a
carboxylic acid of formula (I) can be carried out in the presence
of a coupling agent such as, for instance, carbodiimide, i.e.
1,3-dicyclohexylcarbodiim- ide, 1,3-diisopropylcarbodiimide,
O-(benzotriazol-1-yl)-N,N,N',N'-tetramet- hyluronium
tetrafluoborate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide,
N-cyclohexylcarbodiimide-N'-propyloxymethyl polystyrene or
N-cyclohexylcarbodiimide-N'-methyl polystyrene in a suitable
solvent such as, for instance, dichloromethane, chloroform,
tetrahydrofuran, diethyl ether, 1,4-dioxane, acetonitrile, toluene,
or N,N-dimethylformamide at a temperature ranging from about
-20.degree. C. to reflux for a suitable time, i.e. from about 30
min. to about 96 hours, optionally in the presence of a suitable
catalyst such as 4-dimethylaminopyridine or in the presence of a
further coupling reagent such as N-hydroxybenzotriazole.
[0566] The intermediate compounds of formula (II) wherein R.sub.1
is as hence, represent a further object of the present
invention.
[0567] The compounds of formula (II) wherein R is as described
above and R.sub.1 is hydrogen can be obtained by reacting the
compounds of formula (VII) wherein R is as described above 6
[0568] with a formylating agent such as, for instance,
hexamethylenetetramine in a solvent such as acetic acid at 33% or
phosphorus oxychloride in dimethylformamide, at a temperature
ranging from room temperature to ref lux.
[0569] The compounds of formula (II) wherein R is as described
above and R.sub.1 is alkyl can be prepared by a process
comprising:
[0570] a) reacting the compounds of formula (VII) wherein R is as
described above with methylmagnesium iodide, thus obtaining the
compounds of formula (VIII) 7
[0571] b) reacting them with the compounds of formula (IX)
R.sub.1COCl (IX)
[0572] wherein R.sub.1 is an alkyl group optionally substituted as
above defined, thus obtaining the compounds of formula (X) 8
[0573] wherein R and R.sub.1 are as defined above; and
[0574] c) hydrolyzing the compounds of formula (X) in the presence
of a base.
[0575] The above compounds of formula (VIII) can be prepared in a
suitable solvent such as, for instance, diethylether, dioxane,
tetrahydrofuran, at a temperature ranging from 0.degree. C. to
reflux.
[0576] The above compounds of formula (X), in their turn, can be
prepared in a suitable solvent such as diethylether, dioxane,
tetrahydrofuran, at a temperature ranging from 0.degree. C. to
reflux.
[0577] The hydrolysis according to step (c) can be then carried out
with a suitable base such as sodium hydrate, potassium hydrate,
potassium carbonate in a suitable solvent, for instance mixtures of
methanol/water, ethanol/water, tetrahydrofurane/water, at a
temperature ranging from room temperature to reflux.
[0578] The compounds of formula (VII) where R is amino can be
prepared according to well known methods reported in the
literature. [See, for a reference, Bull. Chem. Soc. Jpn., 65,
2992-2997 (1992); J. AM. Chem. Soc., 81, 743-745 (1959); J. Med.
Chem., 25, 1258-1261 (1982)].
[0579] The compounds of formula (VII) where R is hydroxy, cyano or
halogen can be obtained by conventional methods known in the art,
through nucleophylic substitution of the corresponding diazonium
salts.
[0580] The compounds of formula (VII) where R is --OCOR.sub.4 and
R.sub.4 is as described above can be obtained according to well
known methods from the corresponding compounds of formula (VII)
wherein R is hydroxy, by reaction with the compounds of formula
(XI)
R.sub.4--COOH (XI)
[0581] wherein R.sub.4 is as described above.
[0582] The compound of formula (VII) where R is aminomethyl can be
obtained by reduction of the corresponding cyano derivative, for
instance by using hydrogen in the presence of a suitable catalyst
such as palladium on charcoal, in a solvent such as methanol or
ethanol at room temperature. The compounds of formula (VII) wherein
R is --(CH.sub.2).sub.nNHR.sub.4, n is either 0 or 1 and R.sub.4 is
alkyl, can be obtained from the compounds of formula (VII) wherein
R is --(CH.sub.2).sub.nNH.sub.2 by reaction with a proper
carbonylic compound, in presence of a reductive agent such as
sodiumcyanoborohydride at room temperature and in a solvent such as
methanol or ethanol.
[0583] The compounds of formula (VII) wherein R is NHR.sub.4 and
R.sub.4 is aryl, hence also comprising heteroaryl, can be obtained
from the compounds of formula (VII) where R is halogen by
nucleophylic substitution with the corresponding arylamino
derivative, in solvents such as dioxane, tetrahydrofuran, toluene,
N,N'-dimethylformamide eventually with a base such as potassium
carbonate, triethylamine, N,N-diisopropylethylamine at a
temperature ranging from room temperature to reflux.
[0584] The compounds of formula (VII) where R is
--(CH.sub.2).sub.nNHR.sub- .4, n is 1 and R.sub.4 is aryl, as
above, can be obtained from the compounds of formula (VII) where R
is cyano according to well-known methods requiring the
transformation of the cyano group into a chloromethyl group
followed by nucleophylic substitution with the corresponding
arylamino derivative.
[0585] The compounds of formula (VII) wherein R is
--(CH.sub.2).sub.nNHCOR- .sub.4 and n is either 0 or 1 can be
obtained by reacting the corresponding compounds (VII) wherein R is
--(CH.sub.2).sub.nNH.sub.2 with the compounds of formula (XI)
wherein R.sub.4 is as described above, according to well known
methods.
[0586] The compounds of formula (VII) wherein R is
--(CH.sub.2).sub.nNHCON- H.sub.2 wherein n is either 0 or 1 can be
obtained by reacting the compounds of formula (VII) wherein R is
--(CH.sub.2).sub.nNH.sub.2 with sodium cyanate or potassium cyanate
in mixtures of acetic acid-water at room temperature.
[0587] The compounds of formula (VII) where R is
--(CH.sub.2).sub.nNHCONR.- sub.4R.sub.5 wherein n is either 0 or 1
and R.sub.4 and R.sub.5 are as defined above, can be obtained by a
process comprising:
[0588] a) reacting the compounds of formula (VII) wherein R is
--(CH.sub.2).sub.nNH.sub.2 with 4-nitrophenylchloroformate, thus
obtaining the compounds of formula (XII) wherein n is either 0 or
1: 9
[0589] b) reacting the above compounds (XII) with the compounds of
formula (XIII)
R.sub.4R.sub.5NH (XIII)
[0590] wherein R.sub.4 and R.sub.5 are as defined above.
[0591] The compounds of formula (XII) can be obtained as above
indicated in the presence of a tertiary base such as triethylamine,
N-methylmorpholine, N,N-diisopropylethylamine or pyridine in a
suitable solvent such as toluene, dichloromethane, chloroform,
diethylether, tetrahydrofuran, acetonitrile, dioxane or
N,N-dimethylformamide, at a temperature ranging from about
-20.degree. C. to room temperature.
[0592] The reaction between a compound of formula (XII) and a
compound of formula (XIII) can be carried out in a suitable solvent
such as toluene, dichloromethane, chloroform, diethylether,
tetrahydrofuran, acetonitrile, dioxane or N,N-dimethylformamide, at
a temperature ranging from room temperature to reflux.
[0593] The compounds of formula (VII) where R is
--(CH.sub.2).sub.nNHCOOR.- sub.4 wherein n is either 0 or 1 and
R.sub.4 is as defined above, can be obtained by reacting the
compounds of formula (VII) where R is --(CH.sub.2).sub.nNH.sub.2
with the compounds of formula (XIV):
ClCOOR.sub.4 (XIV)
[0594] wherein R.sub.4 is as defined above, in the presence of a
tertiary base such as triethylamine, N-methylmorpholine,
N,N-diisopropylethylamine or pyridine in a suitable solvent such as
toluene, dichloromethane, chloroform, diethylether,
tetrahydrofuran, acetonitrile, dioxane or N,N-dimethylformamide, at
a temperature ranging from about -10.degree. C. to room
temperature.
[0595] The compounds of formula (VII) where R is
--(CH.sub.2).sub.nNHSO.su- b.2R.sub.4 wherein n is either 0 or 1
and R.sub.4 is as defined above, can be obtained by reacting the
compounds of formula (VII) where R is --(CH.sub.2).sub.nNH.sub.2
with compounds of formula (XV):
ClSO.sub.2R.sub.4 (XV)
[0596] wherein R.sub.4 is as defined above, in the presence of a
tertiary base such as triethylamine, N-methylmorpholine,
N,N-diisopropylethylamine or pyridine in a suitable solvent such as
toluene, dichloromethane, chloroform, diethylether,
tetrahydrofuran, acetonitrile, dioxane or N,N-dimethylformamide, at
a temperature ranging from about -10.degree. C. to room
temperature.
[0597] It is clear to the person skilled in the art that if the
compounds of formula (I), prepared according to the above process
are obtained as an admixture of isomers, hence comprising
stereoisomers or (E,Z) isomers, their separation into the single
isomers of formula (I), carried out according to conventional
techniques, is still within the scope of the present invention.
[0598] Likewise, any admixture of isomers of the compounds of
formula (I) as well as the single isomers are within the scope of
the present invention.
[0599] The conversion of the salt of a compound of formula (I) into
the free compound or, alternatively, of the free compound into a
salt of formula (I), both carried out according to well-known
procedures in the art, is still within the scope of the
invention.
[0600] Other optional conversions of a compound of formula (I) into
another compound of formula (I) can be carried out according to
known methods.
[0601] As an example, an alkylthio or an arylthio group may be
converted into the corresponding alkylsulfonyl and arylsulfonyl
group by reaction, for example, with m-chloroperbenzoic acid in a
suitable solvent such as dichloromethane or chloroform, at a
temperature varying between about -5.degree. C. and room
temperature.
[0602] When preparing the compounds of formula (I) according to the
process object of the present invention, optional functional groups
within both the starting materials or the intermediates thereof,
which could give rise to unwanted side reactions, need to be
properly protected according to conventional techniques.
[0603] Likewise, the conversion of these latter into the free
deprotected compounds may be carried out according to known
procedures.
[0604] The compounds of formula (III), (IV), (V), (VI), (IX),
(XIII), (XIV), (XV), according to the process object of the present
invention, are known compounds or can be obtained according to
known methods.
[0605] The preparation of the compounds of formula (I), according
to the process object of the invention, is preferably carried out
in a serial manner according to combinatorial chemistry techniques
well known to the man skilled in the art.
[0606] As an example, the compounds of formula (I) are prepared by
reacting a given number of compounds of formula (II) in a suitable
solvent with a given number of compounds of formula (III) in a
suitable solvent using supporting reagents and, then, by separating
the resultant compounds from the mixture.
[0607] Whenever appropriate, each of the above compounds of formula
(I) wherein R.sub.3 is a COOH group are transformed into compounds
of formula (I) wherein R.sub.3 is a --COOR.sub.4,
--CONR.sub.4R.sub.5 or CONHR.sub.4 wherein R.sub.4 and R.sub.5 are
as above indicated, by using supporting reagents.
[0608] Pharmacology
[0609] The compounds of formula (I) are active as cdk/cyclin
inhibitors as they gave positive results when tested according to
the following procedure.
[0610] The inhibiting activity of putative cdk/cyclin inhibitors
and the potency of selected compounds was determined through a
method of assay based on the use of the MultiScreen-PH 96 well
plate (Millipore), in which a phosphocellulose filter paper was
placed at each well bottom allowing binding of positive charged
substrate after a washing/filtration step.
[0611] When a radioactivity labelled phosphate moiety was
transferred by the ser/threo kinase to the filter-bound histone,
light emitted was measured in a scintillation counter.
[0612] Inhibition Assay of cdk2/Cyclin A Activity
[0613] Kinase Reaction:
[0614] 1.5 .mu.M histone H1 substrate, 25 .mu.M ATP (0.2 uCi
P33g-ATP), 30 ng of baculovirus co-expressed cdk2/Cyclin A, 10
.mu.M inhibitor in a final volume of 100 .mu.l buffer (TRIS HCl 10
mM pH 7.5, MgCl2 10 mM, 7.5 mM DTT) were added to each well of a 96
U bottom well plate. After 10 min at 37.degree. C incubation,
reaction was stopped by 20 .mu.l EDTA 120 mM.
[0615] Capture:
[0616] 100 .mu.l were transferred from each well to MultiScreen
plate, to allow substrate binding to phosphocellulose filter.
Plates were then washed 3 times with 150 .mu.l/well PBS Ca++/Mg++
free and filtered by MultiScreen filtration system.
[0617] Detection:
[0618] filters were allowed to dry at 37.degree. C., then 100
.mu.l/well scintillant were added and 33P labelled histone H1 was
detected by radioactivity counting in the Top-Count instrument.
[0619] Results:
[0620] data were analysed and expressed as % inhibition referred to
total activity of enzyme (=100%).
[0621] All compounds showing inhibition .gtoreq.50% were further
analysed in order to study and define potency (IC50) as well as the
kinetic-profile of inhibitor through Ki calculation.
[0622] IC50 Determination:
[0623] the protocol used was the same described above, where
inhibitors were tested at different concentrations ranging from
0.0045 to 10 .mu.M. Experimental data were analyzed by the computer
program GraphPad Prizm using the four parameter logistic equation:
y=bottom+(top-bottom)/(1+10 ((logIC50-x)*slope)) where x is the
logarithm of the inhibitor concentration, y is the response; y
starts at bottom and goes to top with a sigmoid shape.
[0624] Ki Calculation:
[0625] either the concentration of ATP and histone H1 substrate
were varied: 4, 8, 12, 24, 48 .mu.M for ATP (containing
proportionally diluted P.sup.33.gamma.-ATP) and 0.4, 0.8, 1.2, 2.4,
4.8 .mu.M for histone were used in absence and presence of two
different, properly chosen inhibitor concentrations.
[0626] Experimental data were analysed by the computer program
"SigmaPlot" for Ki determination, using a random bireactant system
equation: 1 v = V max ( A ) ( B ) aKAKB 1 + ( A ) KA + ( B ) KB + (
A ) ( B ) aKAKB
[0627] where A=ATP and B=histone H1.
[0628] In addition the selected compounds have been characterized
on a panel of ser/threo kinases strictly related to cell cycle
(cdk2/cyclin E, cdk1/cyclin B1, cdk4/Cyclin D1), and for
specificity on MAPK, PKA and EGFR.
[0629] Inhibition Assay of cdk2/Cyclin E Activity
[0630] Kinase Reaction:
[0631] 1.5 .mu.M histone H1 (Sigma # H-5505) substrate, 25 .mu.M
ATP (0.2 .mu.Ci P.sup.33.gamma.-ATP), 15 ng of baculovirus
co-expressed cdk2/GST-Cyclin E, suitable concentrations of
inhibitor in a final volume of 100 .mu.l buffer (TRIS HCl 10 mM pH
7.5, MgCl.sub.2 10 mM, 7.5 mM DTT+ 0.2 mg/ml BSA) were added to
each well of a 96 U bottom well plate. After 10 min at 37.degree.
C. incubation, reaction was stopped by 20 .mu.l EDTA 120 mM.
[0632] Capture:
[0633] 100 .mu.l were transferred from each well to MultiScreen
plate, to allow substrate binding to phosphocellulose filter.
Plates were then washed 3 times with 150 .mu.l/well PBS
Ca.sup.++/Mg.sup.++ free and filtered by MultiScreen filtration
system.
[0634] Detection:
[0635] filters were allowed to dry at 37.degree. C., then 100
.mu.l/well scintillant were added and .sup.33P labelled histone H1
was detected by radioactivity counting in the Top-Count
instrument.
[0636] Inhibition assay of cdk1/Cyclin B1 Activity
[0637] Kinase Reaction:
[0638] 1.5 .mu.M histone H1 (Sigma # H-5505) substrate, 25 .mu.M
ATP (0.2 .mu.Ci P.sup.33.gamma.-ATP), 30 ng of baculovirus
co-expressed cdk1/Cyclin B1, suitable concentrations of inhibitor
in a final volume of 100 .mu.l buffer (TRIS HCl 10 mM pH 7.5,
MgCl.sub.2 10 mM, 7.5 mM DTT+ 0.2mg/ml BSA) were added to each well
of a 96 U bottom well plate. After 10 min at 37.degree. C.
incubation, reaction was stopped by 20 .mu.l EDTA 120 mM.
[0639] Capture:
[0640] 100 .mu.l were transferred from each well to MultiScreen
plate, to allow substrate binding to phosphocellulose filter.
Plates were then washed 3 times with 150 .mu.l/well PBS
Ca.sup.++/Mg.sup.++ free and filtered by MultiScreen filtration
system.
[0641] Detection:
[0642] filters were allowed to dry at 37.degree. C., then 100
.mu.l/well scintillant were added and .sup.33P labelled histone H1
was detected by radioactivity counting in the Top-Count
instrument.
[0643] Inhibition Assay cdk4/Cyclin D1 Activity
[0644] Kinase Reaction:
[0645] 0,4 uM .mu.M mouse GST-Rb(769-921) (# sc-4112 from Santa
Cruz) substrate, 10 .mu.M ATP (0.5 .mu.Ci P.sup.33.gamma.-ATP), 100
ng of baculovirus expressed GST-cdk4/GST-Cyclin D1, suitable
concentrations of inhibitor in a final volume of 50 .mu.l buffer
(TRIS HCl 10 mM pH 7.5, MgCl.sub.2 10 mM, 7.5 mM DTT+ 0.2 mg/ml
BSA) were added to each well of a 96 U bottom well plate. After 40
min at 37.degree. C incubation, reaction was stopped by 20 .mu.l
EDTA 120 mM.
[0646] Capture:
[0647] 60 .mu.l were transferred from each well to MultiScreen
plate, to allow substrate binding to phosphocellulose filter.
Plates were then washed 3 times with 150 .mu.l/well PBS
Ca.sup.++/Mg.sup.++ free and filtered by MultiScreen filtration
system.
[0648] Detection:
[0649] filters were allowed to dry at 37.degree. C., then 100
.mu.l/well scintillant were added and .sup.33P labelled Rb fragment
was detected by radioactivity counting in the Top-Count
instrument.
[0650] Inhibition Assay of MAPK Activity
[0651] Kinase Reaction:
[0652] 10 .mu.M MBP (Sigma # M-1891) substrate, 25 .mu.M ATP (0.2
.mu.Ci P.sup.33.gamma.-ATP), 25 ng of bacterially expressed
GST-MAPK (Upstate Biotechnology # 14-173), suitable concentrations
of inhibitor in a final volume of 100 .mu.l buffer (TRIS HCl 10 mM
pH 7.5, MgCl.sub.2 10 mM, 7.5 mM DTT+ 0.1 mg/ml BSA) were added to
each well of a 96 U bottom well plate. After 15 min at 37.degree.
C. incubation, reaction was stopped by 20 .mu.l EDTA 120 mM.
[0653] Capture:
[0654] 100 .mu.l were transferred from each well to MultiScreen
plate, to allow substrate binding to phosphocellulose filter.
Plates were then washed 3 times with 150 .mu.l/well PBS
Ca.sup.++/Mg.sup.++ free and filtered by MultiScreen filtration
system.
[0655] Detection:
[0656] filters were allowed to dry at 37.degree. C., then 100
.mu.l/well scintillant were added and .sup.33P labelled MBP was
detected by radioactivity counting in the Top-Count instrument.
[0657] Inhibition Assay of PKA Activity
[0658] Kinase Reaction:
[0659] 10 .mu.M histone H1 (Sigma # H-5505) substrate, 10 .mu.M ATP
(0.2 .mu.Ci P.sup.33.gamma.-ATP), 1U of bovine heart PKA (Sigma #
2645), suitable concentrations of inhibitor in a final volume of
100 .mu.l buffer (TRIS HCl 10 mM pH 7.5, MgCl.sub.2 10 mM, 7.5 mM
DTT+ 0.2 mg/ml BSA) were added to each well of a 96 U bottom well
plate. After 5 min at 37.degree. C. incubation, reaction was
stopped by 20 .mu.l EDTA 120 mM.
[0660] Capture:
[0661] 100 .mu.l were transferred from each well to MultiScreen
plate, to allow substrate binding to phosphocellulose filter.
Plates were then washed 3 times with 150 .mu.l/well PBS
Ca.sup.++/Mg.sup.++ free and filtered by MultiScreen filtration
system.
[0662] Detection:
[0663] filters were allowed to dry at 37.degree. C., then 100
.mu.l/well scintillant were added and 3P labelled histone H1 was
detected by radioactivity counting in the Top-Count instrument.
[0664] Inhibition Assay of EGFR Activity
[0665] Kinase Reaction:
[0666] 25 nM in house biotinylated PolyGluTyr (Sigma # 0275)
substrate, 2,5 .mu.m ATP (0.3 .mu.Ci P.sup.33.gamma.-ATP), 80 ng
baculovirus expressed GST-EGFR, suitable concentrations of
inhibitor in a final volume of 100 .mu.l buffer (Hepes 50 mM pH
7,5, MnCl.sub.2-- MgCl.sub.2 3 mM, 1 mM DTT+ 3 .mu.M NaVO3, 0.1
mg/ml BSA) were added to each well of a 96 U bottom well plate.
After 5 min. at 37.degree. C. incubation, reaction was stopped by
20 .mu.l EDTA 120 mM.
[0667] Capture:
[0668] 100 .mu.l were transferred from each well to
streptavidin-Flashplate, to allow biotinylated-substrate binding to
plate. Plates were then washed 3 times with 150 .mu.l/well PBS
Ca.sup.++/Mg.sup.++ free.
[0669] Detection:
[0670] radioactivity counting in the Top-Count instrument.
[0671] In addition, the inhibiting activity of putative cdk/cyclin
inhibitors and the potency of selected compounds was determined
through a method of assay based on the use of a SPA (Scintillation
Proximity Assay) 96 well plate assay. The assay is based on the
ability of streptavidin coated SPA beads to capture a biotinylated
peptide derived from a phosphorylation site of histone.
[0672] When a radioactivity labelled phosphate moiety was
transferred by the ser/threo kinase to the biotinylated histone
peptide, light emitted was measured in a scintillation counter.
[0673] The inhibition assay of cdk5/p25 activity was performed
according to the following protocol:
[0674] Kinase Reaction:
[0675] 1.0 .mu.M biotinylated histone peptide substrate, 0.25 uCi
P33g-ATP, 4 nM cdk5/p25 complex, 0-100 .mu.M inhibitor in a final
volume of 100 .mu.l buffer (Hepes 20 mM pH 7.5, MgCl2 15 mM, 1 mM
DTT) were added to each well of a 96 U bottom well plate. After 20
min at 37.degree. C. incubation, the reaction was stopped by the
addition of 500 ug SPA beads in phosphate-buffered saline
containing 0.1% Triton X-100, 50 uM ATP and 5 mM EDTA. The beads
were allowed to settle, and the radioactivity incorporated in the
33P-labelled peptide was detected in a Top Count scintillation
counter.
[0676] Results:
[0677] Data were analyzed and expressed as % Inhibition using the
formula:
100X(1-(Unknown-Bkgd)/(Enz. Control-Bkgd))
[0678] IC50 values were calculated using a variation of the four
parameter logistics equation:
Y=100/[1+10 ((LogEC50-X)*Slope)]
[0679] Where X=log(uM) and Y=% Inhibition.
[0680] The compounds of formula (I) are therefore useful to
restrict the unregulated proliferation of tumor cells, hence in
therapy in the treatment of various tumors such as, for instance,
carcinomas, e.g. mammary carcinoma, lung carcinoma, bladder
carcinoma, colon carcinoma, ovary and endometrial tumors, sarcomas,
e.g. soft tissue and bone sarcomas, and the hematological
malignancies such as, e.g., leukemias.
[0681] In addition, the compounds of formula (I) are also useful in
the treatment of other cell proliferative disorders such as
psoriasis, vascular smooth cell proliferation associated with
atherosclerosis and post-surgical stenosis and restenosis and in
the treatment of Alzheimer's disease.
[0682] The compounds of the present invention can be administered
either as single agents or, alternatively, in combination with
known anticancer treatments such as radiation therapy or
chemotherapy regimen in combination with cytostatic or cytotoxic
agents, antibiotic-type agents, alkylating agents, antimetabolite
agents, hormonal agents, immunological agents, interferon-type
agents, cyclooxygenase inhibitors (e.g. COX-2 inhibitors),
metallomatrixprotease inhibitors, telomerase inhibitors, tyrosine
kinase inhibitors, anti-growth factor receptor agents, anti-HER
agents, anti-EGFR agents, anti-angiogenesis agents, farnesyl
transferase inhibitors, ras-raf signal transduction pathway
inhibitors, cell cycle inhibitors, other cdks inhibitors, tubulin
binding agents, topoisomerase I inhibitors, topoisomerase II
inhibitors, and the like.
[0683] As an example, the compounds of the invention can be
administered in combination with one or more chemotherapeutic
agents such as, for instance, taxane, taxane derivatives,
encapsulated taxanes, CPT-11, camptothecin derivatives,
anthracycline glycosides, e.g., doxorubicin, idarubicin,
epirubicin, etoposide, navelbine, vinblastine, carboplatin,
cisplatin, estramustine, celecoxib, Sugen SU-5416, Sugen SU-6668,
Herceptin, and the like, optionally within liposomal formulations
thereof.
[0684] If formulated as a fixed dose, such combination products
employ the compounds of this invention within the dosage range
described above and the other pharmaceutically active agent within
the approved dosage range.
[0685] Compounds of formula (I) may be used sequentially with known
anticancer agents when a combination formulation is
inappropriate.
[0686] The compounds of formula (I) of the present invention,
suitable for administration to a mammal, e.g. to humans, can be
administered by the usual routes and the dosage level depends upon
the age, weight, conditions of the patient and the administration
route.
[0687] For example, a suitable dosage adopted for oral
administration of a compound of formula (I) may range from about 10
to about 500 mg pro dose, from 1 to 5 times daily. The compounds of
the invention can be administered in a variety of dosage forms,
e.g. orally, in the form of tablets, capsules, sugar or film coated
tablets, liquid solutions or suspensions; rectally in the form of
suppositories; parenterally, e.g. intramuscularly, or by
intravenous and/or intrathecal and/or intraspinal injection or
infusion.
[0688] The present invention also includes pharmaceutical
compositions comprising a compound of formula (I) or a
pharmaceutically acceptable salt thereof in association with a
pharmaceutically acceptable excipient (which can be a carrier or a
diluent).
[0689] The pharmaceutical compositions containing the compounds of
the invention are usually prepared following conventional methods
and are administered in a pharmaceutically suitable form.
[0690] For example, the solid oral forms may contain, together with
the active compound, diluents, e.g. lactose, dextrose, saccharose,
sucrose, cellulose, corn starch or potato starch; lubricants, e.g.
silica, talc, stearic acid, magnesium or calcium stearate, and/or
polyethylene glycols; binding agents, e.g. starches, arabic gum,
gelatine, methylcellulose, carboxymethylcellulose or polyvinyl
pyrrolidone; disaggregating agents, e.g. a starch, alginic acid,
alginates or sodium starch glycolate; effervescing mixtures;
dyestuffs; sweeteners; wetting agents such as lecithin,
polysorbates, laurylsulphates; and, in general, non-toxic and
pharmacologically inactive substances used in pharmaceutical
formulations. Said pharmaceutical preparations may be manufactured
in known manner, for example, by means of mixing, granulating,
tabletting, sugar-coating, or film-coating processes.
[0691] The liquid dispersions for oral administration may be e.g.
syrups, emulsions and suspensions.
[0692] The syrups may contain as carrier, for example, saccharose
or saccharose with glycerine and/or mannitol and/or sorbitol.
[0693] The suspensions and the emulsions may contain as carrier,
for example, a natural gum, agar, sodium alginate, pectin,
methylcellulose, carboxymethylcellulose, or polyvinyl alcohol.
[0694] The suspension or solutions for intramuscular injections may
contain, together with the active compound, a pharmaceutically
acceptable carrier, e.g. sterile water, olive oil, ethyl oleate,
glycols, e.g. propylene glycol, and, if desired, a suitable amount
of lidocaine hydrochloride.
[0695] The solutions for intravenous injections or infusions may
contain as carrier, for example, sterile water or preferably they
may be in the form of sterile, aqueous, isotonic saline solutions
or they may contain as a carrier propylene glycol.
[0696] The suppositories may contain together with the active
compound a pharmaceutically acceptable carrier, e.g. cocoa butter,
polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester
surfactant or lecithin.
[0697] The following examples are herewith intended to illustrate,
without posing any limitation to, the present invention.
EXAMPLE 1
N-(3-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)acetamide
[0698] 330 mg (2.48 mmol) of 1H-pyrrolo[2,3-b]pyridin-6-ylamine
were dissolved in 15 ml of acetic anhydride and heated at reflux
under stirring. After 6 hours the mixture was cooled down and 50 ml
of aqueous sodium bicarbonate were added. The solution was
maintained under stirring at room temperature for 6 hours, then
extracted with dichloromethane. The organic layer is dried over
sodium sulfate and concentrated under vacuum, leading 480 mg (2.21
mmol; 89% yield) of N-(1-acetyl-1H-pyrrolo[2,3-b]pyr-
idin-6-yl)acetamide. This intermediate was dissolved in 5 ml of
acetic acid 33% in water and 405 mg (2.87 mmol) of
hexamethylenetetramine were added. After 12 hours at 100.degree. C.
the mixture was poured in icy water and basified with aqueous
sodium bicarbonate and extracted with dichloromethane. The organic
layer was then dried over sodium sulfate and evaporated to give 349
mg (60% yield) of the title compound.
[0699] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) .delta. (ppm): 12.8 (s
broad, 1H, NH); 10.39 (s, 1H, NHCO); 9.84 (s, 1H, CHO); 8.31 (d,
J=8.2 Hz, 1H, CH-4); 8.3 (s, 1H, CH-2); 7.32 (d, J=8.2 Hz, 1H,
CH-5); 2.09 (s, 3H, CH.sub.3CO).
[0700] ESI (+) MS: m/z 204 (100, (M+H).sup.+)
[0701] Employing the same method, but starting from
6-chloro-1H-pyrrolo[2,3-b]pyridine, the following compound can be
obtained:
[0702] 6-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde;
[0703] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) .delta. (ppm): 12.8 (s
broad, 1H, NH); 9.9 s, 1H, CHO); 8.47 (s, 1H, CH-2); 8.39 (d, J=8.2
Hz, 1H, CH-4); 7.32 (d, J=8.2 Hz, 1H, CH-5).
[0704] ESI (-) MS: m/z 179 (100, (M+H).sup.-)
[0705] Employing the same method, but starting from
6-bromo-1H-pyrrolo[2,3-b]pyridine, the following compound was
obtained:
[0706] 6-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde;
[0707] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) .delta. (ppm): 12.84 (s
broad, 1H, NH); 9.91 (s, 1H, CHO); 8.46 (s, 1H, CH-2); 8.46 (d,
J=8.2 Hz, 1H, CH-4); 7.45 (d, J=8.2 Hz, 1H, CH-5).
[0708] ESI (-) MS: m/z 225 (100, (M+H).sup.-)
[0709] Employing the same method, but starting from
1H-pyrrolo[2,3-b]pyridin-6-yl benzoate, the following compound was
obtained:
[0710] 3-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl benzoate
[0711] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) .delta. (ppm): 12.8 (s
broad, 1H, NH); 9.93 (s, 1H, CHO); 8.52 (d, J=8.2, 1H, CH-4); 8.48
(s, 1H, CH-2); 8.15 (d, J=8.2 Hz, 2H, orto--CH-phenyl); 7.76 (t,
J=8.2 Hz, 1H, para--CH-phenyl); 7.62 (t, J=8.2 Hz, 2H,
meta-CH-phenyl); 7.21 (d, J=8.2 Hz, 1H, para--CH-phenyl).
[0712] ESI (+) MS: m/z 267 (100, (M+H).sup.+)
EXAMPLE 2
Preparation of
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid
[0713] A mixture of phenylacetic acid (0.0376 mol., 5.1 g) and
1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (0.0376 mol., 5.5 g) in
acetic anhydride (0.1881 mol., 17.7 ml) and Et3N (0.0376 mol., 5.2
ml) was stirred at 100.degree. C., for 6 hrs. The obtained solution
was cooled to 50.degree. C., quenched with conc. hydrochloric acid
(10 ml) and extracted with EtOAc. The organic phase was extracted
with 1 N NaOH.
3-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid was
then precipitated from the aqueous layer with conc. hydrochloric
acid with ice-cooling. Filtration and recrystallization from
isopropyl alcohol of the crude product afforded 4,4 g of the
desired compound as a white solid (44%), m.p.>230.degree. C.
[0714] .sup.1H-NMR (DMSO-d.sub.6) .delta. ppm: 12.3 (s, 1H, COOH);
11.97 (s, 1H, NH pyrrole); 8.19 (dd, 1H, pyridine); 7.99 (s, 1H,
CH.dbd.C); 7.64 (dd, 1H, pyridine); 7.2-7.5 (m, 5H, ph); 7.02 (dd,
1H, pyridine); 6.58 (d, 1H, pyrrole).
[0715] (M+H).sup.+=265
[0716] Analogously, the following compounds can be prepared
starting from the corresponding aldehyde derivatives:
[0717]
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoi-
c acid;
[0718]
3-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0719]
3-(6-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0720]
3-(6-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0721]
3-(6-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0722]
3-[6-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0723]
3-{6-[(methylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl--
2-propenoic acid;
[0724]
3-{6-[(benzylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl--
2-propenoic acid;
[0725]
3-{6-[(benzoylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenoic acid;
[0726]
2-phenyl-3-(6-{[(phenylacetyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenoic acid;
[0727]
3-[6-(benzoyloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propeno-
ic acid;
[0728]
3-[6-(acetyloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propenoi-
c acid;
[0729]
3-[6-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0730]
3-[6-(ethylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propeno-
ic acid;
[0731]
3-[6-(isopropylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
propenoic acid;
[0732]
3-[6-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
propenoic acid;
[0733]
3-(6-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0734]
3-[6-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penoic acid;
[0735]
3-[6-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-
propenoic acid;
[0736]
3-{6-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenoic acid;
[0737]
3-{6-[4-(aminocarbonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenoic acid;
[0738]
3-[6-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenoic
acid;
[0739]
2-phenyl-3-[6-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-p-
ropenoic acid;
[0740]
2-phenyl-3-[6-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl-
]-2-propenoic acid;
[0741]
3-[6-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0742]
3-(6-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenoic acid;
[0743]
3-[6-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0744]
3-[6-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
noic acid;
[0745]
3-{6-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0746]
3-{6-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phe-
nyl-2-propenoic acid;
[0747]
3-{6-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0748]
3-[6-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
noic acid;
[0749]
2-phenyl-3-{6-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-propenoic acid;
[0750]
3-(6-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenoic acid;
[0751]
3-(6-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-phenyl-2-propenoic acid;
[0752]
3-(6-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0753]
2-phenyl-3-{6-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0754]
3-{6-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0755]
3-{6-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0756]
2-phenyl-3-{6-[(2-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0757]
3-{6-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid;
[0758]
3-{6-[([1,1'-biphenyl]-4-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenoic acid;
[0759]
3-{6-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0760]
2-phenyl-3-{6-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0761]
3-{6-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenoic acid;
[0762]
3-(6-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0763]
3-{6-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenoic acid;
[0764]
3-(6-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-phenyl-2-propenoic acid;
[0765]
3-(6-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0766]
3-(6-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0767]
2-phenyl-3-{6-[(1-piperidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyrid-
in-3-yl}-2-propenoic acid;
[0768]
2-phenyl-3-{6-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0769]
3-(6-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-phenyl-2-propenoic acid;
[0770]
3-{6-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0771]
3-{6-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0772]
3-{6-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0773]
3-{6-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0774]
2-phenyl-3-{6-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-propenoic acid;
[0775]
2-phenyl-3-(6-{[(phenylsulfonyl)methyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-propenoic acid;
[0776]
3-(6-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0777]
3-{6-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid;
[0778]
3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0779]
3-(4-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0780]
3-[4-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penoic acid;
[0781]
3-[4-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenoic acid;
[0782]
3-{4-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenoic acid;
[0783]
3-{4-[4-(aminocarbonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenoic acid;
[0784]
3-[4-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penoic acid;
[0785]
2-phenyl-3-[4-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-p-
ropenoic acid;
[0786]
2-phenyl-3-[4-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl-
]-2-propenoic acid;
[0787]
3-(4-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0788]
3-[4-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0789]
3-[4-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openoic acid;
[0790]
3-[4-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0791]
3-(4-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenoic acid;
[0792]
3-[4-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0793]
3-[4-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
noic acid;
[0794]
3-{4-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0795]
3-{4-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phe-
nyl-2-propenoic acid;
[0796]
3-{4-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0797]
3-[4-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
noic acid;
[0798]
2-phenyl-3-{4-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-propenoic acid;
[0799]
3-(4-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenoic acid;
[0800]
3-(4-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-phenyl-2-propenoic acid;
[0801]
3-(4-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0802]
2-phenyl-3-{4-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0803]
3-{4-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0804]
3-{4-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0805]
2-phenyl-3-{4-[(3-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0806]
3-{4-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid;
[0807]
3-{4-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0808]
2-phenyl-3-{4-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0809]
3-{4-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenoic acid;
[0810]
3-(4-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0811]
3-{4-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenoic acid;
[0812]
3-(4-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-phenyl-2-propenoic acid;
[0813]
3-(4-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0814]
3-(4-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0815]
2-phenyl-3-{4-[(1-piperidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyrid-
in-3-yl}-2-propenoic acid;
[0816]
2-phenyl-3-{4-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0817]
3-(4-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-phenyl-2-propenoic acid;
[0818]
3-{4-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0819]
3-{4-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0820]
3-{4-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0821]
3-{4-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0822]
2-phenyl-3-{4-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-propenoic acid;
[0823]
3-{4-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0824]
3-{4-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid;
[0825]
3-(4-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0826]
3-(5-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic
acid;
[0827] 3-[5-
(methylamino)-H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen- oic
acid;
[0828]
3-[5-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]2-2-phenyl-2-p-
ropenoic acid;
[0829]
3-[5-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0830]
3-(5-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenoic acid;
[0831]
3-[5-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
oic acid;
[0832]
3-[5-(benzoylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
noic acid;
[0833]
3-{5-[(4-bromobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0834]
3-{5-[(3-hydroxybenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phe-
nyl-2-propenoic acid;
[0835]
3-{5-[(3-aminobenzoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0836]
3-[5-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
noic acid;
[0837]
2-phenyl-3-{5-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-propenoic acid;
[0838]
3-(5-([(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenoic acid;
[0839]
3-(5-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-phenyl-2-propenoic acid;
[0840]
3-(5-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0841]
2-phenyl-3-{5-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0842]
3-{5-[(1H-indol-3-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0843]
3-{5-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0844]
2-phenyl-3-{5-[(3-thienylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenoic acid;
[0845]
(2E)-3-{5-[([1,1'-biphenyl]-4-ylcarbonyl)amino]-1H-pyrrolo[2,3-b]py-
ridin-3-yl}-2-phenyl-2-propenoic acid;
[0846]
3-{5-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0847]
2-phenyl-3-{5-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0848]
3-{5-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenoic acid;
[0849]
3-(5-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0850]
3-{5-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenoic acid;
[0851]
3-(5-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-phenyl-2-propenoic acid;
[0852]
3-(5-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenoic acid;
[0853]
3-(5-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenoic acid;
[0854]
2-phenyl-3-{5-[(1-piperidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyrid-
in-3-yl}-2-propenoic acid;
[0855]
2-phenyl-3-{5-[(1-pyrrolidinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenoic acid;
[0856]
3-(5-{[(4-methyl-1-piperazinyl)carbonyl]amino}-1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-phenyl-2-propenoic acid;
[0857]
3-{5-[(4-morpholinylcarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenoic acid;
[0858]
3-{5-[(ethoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0859]
3-{5-[(tert-butoxycarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenoic acid;
[0860]
3-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0861]
2-phenyl-3-{5-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-propenoic acid;
[0862]
3-{5-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenoic acid;
[0863]
3-{5-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenoic acid;
[0864]
3-(5-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenoic acid;
[0865]
2-(4-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0866] 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(4-tolyl)-2-propenoic
acid
[0867]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[2-(trifluoromethyl)phenyl]-2-p-
ropenoic acid
[0868]
2-(1-acetyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enoic acid
[0869]
2-(1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0870]
2-(3-fluoro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid
[0871]
2-(2,3-dihydro-1H-inden-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenoic acid
[0872]
2-(3-pyridinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0873]
2-(4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0874]
2-(4-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0875]
2-(2-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0876]
2-(2-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0877]
2-[1,1'-biphenyl]-4-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0878]
2-(4-hydroxy-5-isopropyl-2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenoic acid
[0879]
2-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenoic acid
[0880]
2-(3-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0881]
2-(3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0882]
2-(3-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0883]
2-(1,3-benzodioxol-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
oic acid
[0884]
2-(3,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno-
ic acid
[0885]
2-(3-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0886]
2-(4-butoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0887]
2-(3-chloro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid
[0888]
2-[4-(methylsulfonyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid
[0889]
2-(4-ethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0890]
2-(3-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0891]
2-(2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0892]
2-(3,4-dihydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno-
ic acid
[0893] 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(2-thienyl)-2-propenoic
acid
[0894]
2-(2-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0895]
2-(2-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0896]
2-(2-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0897]
2-(2,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0898]
2-(2-chloro-6-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid
[0899]
2-(2,6-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0900]
2-(2,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno-
ic acid
[0901]
2-(3,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0902]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3,4,5-trimethoxyphenyl)-2-prop-
enoic acid
[0903]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[3-(trifluoromethyl)phenyl]-2-p-
ropenoic acid
[0904]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethyl)phenyl]-2-p-
ropenoic acid
[0905]
2-[3,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenoic acid
[0906]
2-(2,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0907]
2-(2,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0908]
2-(3,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0909]
2-(3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoi-
c acid
[0910]
2-[4-(benzyloxy)-3-methoxyphenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid
[0911] 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3-thienyl)-2-propenoic
acid
[0912]
2-(5-methoxy-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penoic acid
[0913] 2-(1-naphthyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0914]
2-(3-methyl-1-benzothien-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenoic acid
[0915]
2-(3,4-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propeno-
ic acid
[0916]
2-(4-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0917]
2-[4-(acetylamino)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope-
noic acid
[0918]
2-[4-amino-phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0919]
2-(5-bromo-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope-
noic acid
[0920]
2-(1-methyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enoic acid
[0921]
2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0922]
2-[2,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenoic acid
[0923]
2-(2,3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
oic acid
[0924]
2-[5-(benzyloxy)-1H-indol-3-yl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenoic acid
[0925]
2-(2-amino-1,3-thiazol-4-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid
[0926] 2-mesityl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0927]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethoxy)phenyl]-2--
propenoic acid
[0928]
2-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenoic acid
[0929]
2-[4-(2-amino-2-oxoethoxy)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenoic acid
[0930]
2-{4-[2-oxo-2-(1-pyrrolidinyl)ethoxy]phenyl}-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenoic acid
[0931]
2-(3-hydroxy-5-methoxy-2-propylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenoic acid
[0932]
2-(4-phenoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoic
acid
[0933]
2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenoic acid
[0934]
2-{3-[(methylsulfonyl)amino]phenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-propenoic acid
[0935]
2-{4-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-propenoic acid
[0936]
2-[4-(1-pyrrolidinyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openoic acid
[0937]
2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenoic acid.
EXAMPLE 3
Preparation of
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[0938] To a solution of 264 mg (1 mmol.) of
3-(1H-pyrrolo[2,3-b]pyridin-3-- yl)-2-phenyl-2-propenoic acid in
1.5 ml of THFd and 3 ml of DMFd was added 350 .mu.l of
N,N-diisopropylethylamine and 154 mg (1.4 mmol.) of
N-hydroxybenzotriazole ammonium salt. The obtained mixture was
cooled to -20.degree. C. and 266 mg (1.4 mmol.) of
1-(3-dimethylaminopropyl)-3-ethy- lcarbodiimide were added. The
reaction mixture was stirred for 2 hours at -20.degree. C. and then
warmed to room temperature. After additional 12 hours, the organic
layer was diluted with dichloromethane, washed with saturated
sodium bicarbonate, brine, dried over sodium sulphate and
evaporated. The residual solid was triturated with EtOAc to afford
76 mg of the title compound as a white solid (yield 29%) m.p.
222-224.degree. C.
[0939] .sup.1H-NMR (DMSO-d6) .delta.ppm: 11.79 (s, 1H, NH pyrrole);
8.19 (dd, 1H, pyridine); 7.82 (dd, 1H, pyridine); 7.76 (s, 1H,
CH.dbd.C); 7.2-7.5 (m, 5H, ph); 7.04 (dd, 1H, pyridine); 6.3 (d,
1H, pyrrole); 7.1 (s, 1H, CONH.sub.2); 6.7 (s, 1H, CONH.sub.2).
[0940] (M+H).sup.+=264
[0941] Analogously the following compounds can be prepared starting
from the corresponding carboxylic acid:
[0942]
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenam-
ide;
[0943]
3-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0944]
3-(6-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0945]
3-(6-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0946]
3-(6-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0947]
3-[6-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide;
[0948]
3-{6-[(methylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl--
2-propenamide;
[0949]
3-{6-[(benzylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl--
2-propenamide;
[0950]
N-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin--
6-yl)methyl)benzamide;
[0951]
2-phenyl-3-(6-{[(phenylacetyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide;
[0952]
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl
benzoate;
[0953]
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl
acetate;
[0954]
3-[6-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide;
[0955]
3-[6-(ethylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propena-
mide;
[0956]
3-[6-(isopropylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penamide;
[0957]
3-[6-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide;
[0958]
3-(6-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide;
[0959]
3-[6-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penamide;
[0960]
3-[6-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide;
[0961]
3-{6-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenamide;
[0962]
4-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin--
6-yl}amino)benzamide;
[0963]
3-[6-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamide;
[0964]
2-phenyl-3-[6-(3-pyridinylamino)-1H-pyrrolo[2,3-blpyridin-3-yl]-2-p-
ropenamide;
[0965]
2-phenyl-3-[6-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl-
]-2-propenamide;
[0966]
3-[6-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide;
[0967]
3-(6-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenamide;
[0968]
3-[6-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide;
[0969]
3-{6-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenamide;
[0970]
3-(6-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide;
[0971]
3-{6-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenamide;
[0972]
3-(6-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-phenyl-2-propenamide;
[0973]
3-(6-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide;
[0974]
3-(6-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide;
[0975]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-1-piperidinecarboxamide;
[0976]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-4-methyl-1-piperazinecarboxamide;
[0977]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-4-morpholinecarboxamide;
[0978]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-1-pyrrolidinecarboxamide;
[0979] ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridi-
n-6-ylcarbamate;
[0980] tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]p-
yridin-6-ylcarbamate;
[0981]
3-{6-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenamide;
[0982]
2-phenyl-3-{6-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-propenamide;
[0983]
2-phenyl-3-(6-{[(phenylsulfonyl)methyl]amino}-1H-pyrrolo[2,3-b]pyri-
din-3-yl)-2-propenamide;
[0984]
3-(6-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenamide;
[0985]
3-{6-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenamide;
[0986]
3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[0987]
3-(4-anilino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[0988]
3-[4-(4-bromoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penamide
[0989]
3-[4-(3-hydroxyanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-p-
ropenamide
[0990]
3-{4-[4-(aminosulfonyl)anilino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-ph-
enyl-2-propenamide
[0991]
4-({3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin--
4-yl}amino)benzamide
[0992]
3-[4-(3-aminoanilino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pro-
penamide
[0993]
2-phenyl-3-[4-(3-pyridinylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-p-
ropenamide
[0994]
2-phenyl-3-[4-(1,3-thiazol-2-ylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl-
]-2-propenamide
[0995]
3-(4-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[0996]
3-[4-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide
[0997]
3-[4-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide
[0998]
3-[4-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide
[0999]
3-(4-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenamide
[1000]
3-[4-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide
[1001]
3-{4-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenamide
[1002]
3-(4-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide
[1003]
3-{4-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenamide
[1004]
3-(4-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-phenyl-2-propenamide
[1005]
3-(4-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide
[1006]
3-(4-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide
[1007]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}-1-piperidinecarboxamide
[1008]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}-1-pyrrolidinecarboxamide
[1009]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}-4-methyl-1-piperazinecarboxamide
[1010]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}-4-morpholinecarboxamide
[1011] 1-ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-ylcarbamate
[1012] 1- tert-butyl 3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H
pyrrolo[2,3-b]pyridin-4-ylcarbamate
[1013]
3-{4-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenamide
[1014]
2-phenyl-3-{4-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-propenamide
[1015]
3-{4-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenamide
[1016]
3-{4-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenamide
[1017]
3-(4-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenamide
[1018]
3-(5-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[1019]
3-[5-(methylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide
[1020]
3-[5-(cyclohexylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-pr-
openamide
[1021]
3-[5-(benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide
[1022]
3-(5-{[4-(aminosulfonyl)benzyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenamide
[1023]
3-[5-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-propen-
amide
[1024]
3-{5-[(aminocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phenyl-
-2-propenamide
[1025]
3-(5-{[(methylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide
[1026]
3-{5-[(anilinocarbonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phen-
yl-2-propenamide
[1027]
3-(5-{[(4-bromoanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-phenyl-2-propenamide
[1028]
3-(5-{[(3-hydroxyanilino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-
-yl)-2-phenyl-2-propenamide
[1029]
3-(5-{[(benzylamino)carbonyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide
[1030]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-1-piperidinecarboxamide
[1031]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-1-pyrrolidinecarboxamide
[1032]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-4-methyl-1-piperazinecarboxamide
[1033]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-4-morpholinecarboxamide
[1034] ethyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridi-
n-5-ylcarbamate
[1035] tert-butyl
3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]p-
yridin-5-ylcarbamate
[1036]
3-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenamide
[1037]
2-phenyl-3-{5-[(phenylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl-
}-2-propenamide
[1038]
3-{5-[(benzylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-pheny-
l-2-propenamide
[1039]
3-{5-[([1,1'-biphenyl]-4-ylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-
-3-yl}-2-phenyl-2-propenamide
[1040]
3-(5-{[([1,1'-biphenyl]-4-ylmethyl)sulfonyl]amino}-1H-pyrrolo[2,3-b-
]pyridin-3-yl)-2-phenyl-2-propenamide
[1041]
2-(4-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1042]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(4-tolyl)-2-propenamide
[1043]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[2-(trifluoromethyl)phenyl]-2-p-
ropenamide
[1044]
2-(1-acetyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enamide
[1045]
2-(1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1046]
2-(3-fluoro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)
-2-propenamide
[1047]
2-(2,3-dihydro-1H-inden-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenamide
[1048]
2-(3-pyridinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1049]
2-(4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1050]
2-(4-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1051]
2-(2-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1052]
2-(2-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1053]
2-[1,1'-biphenyl]-4-yl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1054]
2-(4-hydroxy-5-isopropyl-2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridi-
n-3-yl)-2-propenamide
[1055]
2-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-p-
ropenamide
[1056]
2-(3-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1057]
2-(3-methoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1058]
2-(3-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1059]
2-(1,3-benzodioxol-5-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide
[1060]
2-(3,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide
[1061]
2-(3-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1062]
2-(4-butoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1063]
2-(3-chloro-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1064]
2-[4-(methylsulfonyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1065]
2-(4-ethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1066]
2-(3-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1067]
2-(2-methylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1068]
2-(3,4-dihydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide
[1069]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(2-thienyl)-2-propenamide
[1070]
2-(2-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1071]
2-(2-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1072]
2-(2-chlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1073]
2-(2,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1074]
2-(2-chloro-6-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide
[1075]
2-(2,6-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1076]
2-(2,5-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide
[1077]
2-(3,4-dichlorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1078]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3,4,5-trimethoxyphenyl)-2-prop-
enamide
[1079]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[3-(trifluoromethyl)phenyl]-2-p-
ropenamide
[1080]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethyl)phenyl]-2-p-
ropenamide
[1081]
2-[3,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenamide
[1082]
2-(2,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1083]
2-(2,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1084]
2-(3,4-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1085]
2-(3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenam-
ide
[1086]
2-[4-(benzyloxy)-3-methoxyphenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide
[1087]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(3-thienyl)-2-propenamide
[1088]
2-(5-methoxy-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide
[1089]
2-(1-naphthyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1090]
2-(3-methyl-1-benzothien-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2--
propenamide
[1091]
2-(3,4-dimethoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propena-
mide
[1092]
2-(4-bromophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1093]
2-[4-(acetylamino)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope-
namide
[1094]
2-[4-amino-phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1095]
2-(5-bromo-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prope-
namide
[1096]
2-(1-methyl-1H-indol-3-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enamide
[1097]
2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1098]
2-[2,5-bis(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-propenamide
[1099]
2-(2,3,5-difluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide
[1100]
2-[5-(benzyloxy)-1H-indol-3-yl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenamide
[1101]
2-(2-amino-1,3-thiazol-4-yl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1102]
2-mesityl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1103]
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[4-(trifluoromethoxy)phenyl]-2--
propenamide
[1104]
2-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenamide
[1105]
2-[4-(2-amino-2-oxoethoxy)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-propenamide
[1106]
2-{4-[2-oxo-2-(1-pyrrolidinyl)ethoxy]phenyl}-3-(1H-pyrrolo[2,3-b]py-
ridin-3-yl)-2-propenamide
[1107]
2-(3-hydroxy-5-methoxy-2-propylphenyl)-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenamide
[1108]
2-(4-phenoxyphenyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1109]
2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenamide
[1110]
2-{3-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-propenamide
[1111]
2-{4-[(methylsulfonyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-3-y-
l)-2-propenamide
[1112]
2-[4-(1-pyrrolidinyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1113]
2-{4-[(2-amino-2-oxoethyl)amino]phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-
-3-yl)-2-propenamide
EXAMPLE 4
Preparation of
N-butyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propen-
amide
[1114] To a solution of
3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-prope- noic acid (100
mg, 0.3784 mmol.) in 2 ml of DMFd were added
O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoborate
(121.5 mg, 0.3784 mmol.), N-hydroxybenzotriazole (51.1 mg, 0.3784
mmol) and N,N-diisopropylethylamine (129.2 .mu.l, 0.7568 mmol).
After stirring at room temperature for 30 min., 34.5 .mu.l (0.3784
mmol.) of n-butylamine were added and the obtained solution was
stirred at room temperature, for 24 hours. The resulting mixture
was concentrated by evaporation of the solvent in vacuo, the
residue was diluted with dichloromethane washed with 1 N NaOH, 1 N
HCl, brine, dried over sodium sulphate and evaporated. The residual
solid was triturated with Et2O to afford 49 mg of the title
compound as a white solid (yield 41%) m.p. 177-179.degree. C.
(dec.)
[1115] .sup.1H-NMR (DMSO-d.sub.6) .delta. ppm: 11.85 (s, 1H, NH
pyrrole); 8.21 (dd, 1H, pyridine); 7.82 (dd, 1H, pyridine); 7.7 (s,
1H, CH.dbd.C); 7.2-7.5 (m, 5H, ph); 7.08 (dd, 1H, pyridine); 6.35
(d, 1H, pyrrole); 7.05 (s, 1H, CONH); 3.14 (m, 2H,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3); 1.4 (m, 2H,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3); 1.24 (m, 2H,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3); 0.86 (t, 3H,
CH.sub.2CH.sub.2CH.sub.2C- H.sub.3).
[1116] (M+H).sup.+=320
[1117] Analogously the following compounds can be prepared starting
from 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenoic acid
and the suitable amine:
[1118]
N-benzyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1119]
N-methyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1120]
N-(4-methoxyphenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1121]
1-(4-morpholinyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
en-1-one
[1122]
N-(4-chlorophenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide
[1123]
N,N-dimethyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenami-
de
[1124]
N-isopropyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamid-
e
[1125]
2-phenyl-1-(1-piperidinyl)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
en-1-one
[1126]
N,N-[(3-aminomethyl)-pyridin]-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin--
3-yl)-2-propenamide
[1127]
N-benzyl-N-methyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-prop-
enamide
[1128]
N-(1H-indazol-6-yl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1129]
N-(4-methoxybenzyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1130]
N-(4-chlorobenzyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide
[1131]
N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-phenyl-3-(1H-pyrrolo[2,3-b]pyr-
idin-3-yl)-2-propenamide
[1132]
N-furfuryl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1133]
N-(4-hydroxypiperidin)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenamide
[1134]
N-(3-hydroxypiperidin)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-
-propenamide
[1135]
N-(3-methoxyphenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pr-
openamide
[1136]
N,2-diphenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1137]
3-[3-(4-methyl-1-piperazinyl)-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo-
[2,3-b]pyridine
[1138]
N-[4-(dimethylamino)phenyl]-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3--
yl)-2-propenamide
[1139]
N-(3-chlorophenyl)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pro-
penamide
[1140]
N,N-diethyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamid-
e
[1141]
3-[3-(4-benzyl-1-piperazinyl)-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo-
[2,3-b]pyridine
[1142]
2-[2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoyl]-1,2,3,4--
tetrahydroisoquinoline
[1143]
N-(tert-butoxy)-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propen-
amide
[1144]
N-hydroxy-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
EXAMPLE 5
3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[1145] 1 g (3.13 mmol) of
3-(6-acetylamino-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide was dissolved in 20 ml of methanol and 3.13
ml of sodium hydrate 1 M were added. The solution is maintained at
room temperature for 5 hours and then concentrated under vacuum.
The residue was redissolved with dichloromethane and washed with
water. The organic layer was finally dried over sodium sulfate and
evaporated to give 696 mg (80% yield) of the title compound.
EXAMPLE 6
3-{6-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-prope-
namide
[1146] 500 mg (3.67 mmol) of phenylacetic acid were dissolved in 20
ml of dichloromethane and 705 mg (3.67 mmol) of
N-(3-dimethylaminopropyl)-N'-et- hylcarbodiimide hydrochloride were
added at 0.degree. C. The mixture is maintained at the same
temperature for 30 minutes and then a solution of 680 mg (2.44
mmol) of 3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl--
propenamide in 10 ml of dichloromethane was added dropwise. After 6
hours at room temperature the mixture was washed with aqueous
sodium bicarbonate. The organic layer was dried over sodium sulfate
and evaporated. The residue was chromatographed on a silica gel
column by using a mixture cyclohexane/ethylacetate 4/1 to give 626
mg (65% yield) of the title compound.
[1147] Analogously the following compounds can be prepared starting
from
3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
and the suitable carboxylic acid:
[1148]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}benzamide;
[1149]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-4-bromobenzamide;
[1150]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-3-hydroxybenzamide;
[1151]
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]p-
yridin-6-yl}benzamide;
[1152]
3-[6-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
namide;
[1153]
2-phenyl-3-{6-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-propenamide;
[1154]
3-(6-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenamide;
[1155]
3-(6-([(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-phenyl-2-propenamide;
[1156]
3-(6-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide;
[1157]
2-phenyl-3-{6-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenamide;
[1158]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl}-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-1H-indole-3-carboxamide;
[1159]
3-{6-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide;
[1160]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}-2-thiophenecarboxamide;
[1161]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-6-
-yl}[1,1'-biphenyl]-4-carboxamide;
[1162]
3-{6-[([1,1'-biphenyl]-4-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenamide;
[1163]
3-{.sup.6-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-phenyl-2-propenamide;
[1164]
2-phenyl-3-{6-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenamide;
[1165] N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo
[2,3-b]pyridin-4-yl}benzamide
[1166]
N-{3-[.sup.3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}-4-bromobenzamide
[1167]
N-{3-[.sup.3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyri-
din-4-yl}-3-hydroxybenzamide
[1168]
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]p-
yridin-4-yl}benzamide
[1169]
3-[4-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
namide
[1170]
2-phenyl-3-{4-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-propenamide
[1171]
3-(4-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-.sup.2-phenyl-2-propenamide
[1172]
3-(4-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-
-2-phenyl-2-propenamide
[1173]
3-(4-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide
[1174]
2-phenyl-3-{4-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenamide
[1175]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}-1H-indole-3-carboxamide
[1176]
3-{4-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide
[1177]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}-2-thiophenecarboxamide
[1178]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-4-
-yl}[1,11-biphenyl]-4-carboxamide
[1179]
3-{4-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenamide
[1180]
2-phenyl-3-{4-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenamide
[1181]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}benzamide
[1182]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-4-bromobenzamide
[1183]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-3-hydroxybenzamide
[1184]
3-amino-N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]p-
yridin-5-yl}benzamide
[1185]
3-[5-(butyrylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-phenyl-2-prope-
namide
[1186]
2-phenyl-3-{5-[(phenylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-propenamide
[1187]
3-(5-{[(3-hydroxyphenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl-
)-2-phenyl-2-propenamide
[1188] 3-(5-{[(3-chlorophenyl)acetyl]amino}-1H-pyrrolo[2,3-35
b]pyridin-3-yl)-2-phenyl-2-propenamide
[1189]
3-(5-{[(3-aminophenyl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)--
2-phenyl-2-propenamide
[1190]
2-phenyl-3-{5-[(3-pyridinylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-
-yl}-2-propenamide
[1191]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-1H-indole-3-carboxamide
[1192]
3-{5-[(1H-indol-3-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2--
phenyl-2-propenamide
[1193]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}-2-thiophenecarboxamide
[1194]
N-{3-[3-amino-3-oxo-2-phenyl-1-propenyl]-1H-pyrrolo[2,3-b]pyridin-5-
-yl}[1,1'-biphenyl]-4-carboxamide
[1195]
3-{5-[(1,3-oxazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}--
2-phenyl-2-propenamide
[1196]
2-phenyl-3-(5-[(1,3-thiazol-2-ylacetyl)amino]-1H-pyrrolo[2,3-b]pyri-
din-3-yl}-2-propenamide
[1197]
3-{6-[(2-naphthylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phe-
nyl-2-propenamide
[1198]
2-(3-chloro-4-hydroxyphenyl)-3-{6-[(2-naphthylacetyl)amino]-1H-pyrr-
olo [2,3-b]pyridin-3-yl}-2-propenamide
[1199]
3-{6-[(1-naphthylacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}-2-phe-
nyl-2-propenamide
[1200]
2-(3-chloro-4-hydroxyphenyl)-3-{6-[(1-naphthylacetyl)amino]-1H-pyrr-
olo[2,3-b]pyridin-3-yl}-2-propenamide
[1201]
2-phenyl-3-[6-({[4-(2-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[2,3-b-
]pyridin-3-yl]-2-propenamide
[1202]
2-(3-chloro-4-hydroxyphenyl)-3-[6-({[4-(2-thienyl)phenyl]acetyl}ami-
no )-1H-pyrrolo[2,3-b]-pyridin-3-yl]-2-propenamide
[1203]
2-phenyl-3-[6-({[4-(3-thienyl)phenyl]acetyl}amino)-1H-pyrrolo[2,3-b-
]pyridin-3-yl]-2-propenamide
[1204]
2-(3-chloro-4-hydroxyphenyl)-3-[6-({[4-(3-thienyl)phenyl]acetyl}ami-
no)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-propenamide
[1205]
3-(6-{[(3',4'-difluoro[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo-
[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[1206]
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(3',4'-difluoro[1,1'-biphenyl]--
4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1207]
3-(6-{[(5'-fluoro-2'-methoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-p-
yrrolo[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[1208]
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(5'-fluoro-2'-methoxy[1,1'-biph-
enyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1209]
3-(6-{[(2',5'-difluoro[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo-
[2,3-b]pyridin-3-yl)-2-phenyl-2-propenamide
[1210]
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(2',5'-difluoro[1,1'-biphenyl]--
4-yl)acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide
[1211]
3-(6-{[(3'-ethoxy[1,1'-biphenyl]-4-yl)acetyl]amino}-1H-pyrrolo[2,3--
b]pyridin-3-yl)-2-phenyl-2-propenamide
[1212]
2-(3-chloro-4-hydroxyphenyl)-3-(6-{[(3'-ethoxy[1,1'-biphenyl]-4-yl)-
acetyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenamide.
[1213] All compounds were characterized by mass spectrometry (MS).
LC-MS confirmed that in each case the principle component had a
molecular ion corresponding to the expected product.
[1214] The compounds showed an HPLC area % ranging from 78 to
100.
[1215] HPLC analysis:
[1216] Solvent A: H2O/CH3CN=90/10+0.1% TFA
[1217] Solvent B: H2O/CH3CN=10/90+0.075% TFA
1 Time (min) % A % B 0 0 100 6.5 0 100 7 100 0 10 100 0
[1218] Rate: 1.5 ml/min
[1219] Detection: UV 254 nm
[1220] Temperature: room temperature
[1221] Column: Supelco.TM., Discovery RP Amide C16, 5.quadrature.m,
(50.times.4.6) mm
* * * * *