U.S. patent application number 10/611091 was filed with the patent office on 2004-01-29 for derivatives of monosaccharides as cell adhesion inhibitors.
Invention is credited to Arora, Sudershan K., Gupta, Jang Bahadur, Joshi, Vishwas D..
Application Number | 20040018995 10/611091 |
Document ID | / |
Family ID | 11088155 |
Filed Date | 2004-01-29 |
United States Patent
Application |
20040018995 |
Kind Code |
A1 |
Arora, Sudershan K. ; et
al. |
January 29, 2004 |
Derivatives of monosaccharides as cell adhesion inhibitors
Abstract
This invention relates generally to compounds and processes for
synthesizing derivatives of
2-3-O-isopropylidene-.alpha.-L-xylo-2-hexulof- uranosonic acid. The
compounds of this invention are useful, inter-alia, for the
inhibition and prevention of cell adhesion and cell
adhesion-mediated pathologies, including inflammatory and
autoimmune diseases, such as bronchial asthma, rheumatoid
arthritis, type I diabetes, multiple sclerosis, allograft rejection
and psoriasis. This invention also relates to pharmacological
compositions containing derivatives of
2-3-O-isopropylidene-.alpha.-L-xylo-2-hexulofuranosonic acid and
the methods of treating such pathologies as listed above.
Inventors: |
Arora, Sudershan K.;
(Gurgaon, IN) ; Gupta, Jang Bahadur; (Gurgaon,
IN) ; Joshi, Vishwas D.; (New Delhi, IN) |
Correspondence
Address: |
Jay R. Deshmukh
Ranbaxy Pharmaceuticals, Inc.
Suite 2100
600 College Road, East
PRINCETON
NJ
08540
US
|
Family ID: |
11088155 |
Appl. No.: |
10/611091 |
Filed: |
July 1, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10611091 |
Jul 1, 2003 |
|
|
|
09276368 |
Mar 25, 1999 |
|
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6590085 |
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Current U.S.
Class: |
514/42 ;
536/18.7; 536/53 |
Current CPC
Class: |
A61P 3/10 20180101; C07H
9/04 20130101; A61P 41/00 20180101; A61P 25/28 20180101; A61P 37/00
20180101; A61P 29/00 20180101; A61P 19/02 20180101; A61P 11/06
20180101; A61P 17/06 20180101; A61P 37/06 20180101; A61P 25/00
20180101 |
Class at
Publication: |
514/42 ;
536/18.7; 536/53 |
International
Class: |
A61K 031/7052; A61K
031/7024; C07H 005/06 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 15, 1999 |
IN |
86/DEL/99 |
Claims
1. Compounds having the structure of Formula I: 6and their
pharmaceutically acceptable salts esters, enantiomers,
diastereomers, N-oxides, amides, prodrugs, metabolites or
polymorphs, wherein R is C.sub.1 to C.sub.1-5 alkyl, alkene, alkyne
(straight chain or branched), aryl, substituted aryl or alkylaryl
and R.sub.1 is phenyl o-, m- or p-chlorophenyl, tolyl,
methoxyphenyl or nitrophenyl and R.sub.2 is H, pyrrolidinyl,
piperidinyl, morpholinyl or hexamethyleneimino or a radical of the
formula NHR.sub.3, wherein R.sub.3 is C.sub.1 to C.sub.1-5 alkyl,
alkene or alkyne (straight chain or branched) or a radical of
Formula III: 7wherein n is a whole number up to 5 and 8is a five-,
six- or seven-membered heterocyclic ring containing one or more
heteroatoms.
2. The compounds of claim 1, wherein 9is pyrrolidinyl, piperidinyl,
morpholinyl or hexamethyleneimino.
3. Compounds according to claim 1 selected from the group
consisting of:
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-pyrrolidinyl-
-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(methy-
lcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6-pyrrolidin-
yl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-c-
hlorophenylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofurano-
se
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-pyrroli-
dinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(-
p-methoxyphenylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofu-
ranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-d-
ecyl-4-(phenylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofur-
anose
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-
-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dec-
yl-4-(p-tolylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofura-
nose
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-
-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dec-
yl-4-(p-nitrophenylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexu-
lofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-p-
yrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-hepty-
l-4-(p-chlorophenylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexu-
lofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-hept-
yl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-he-
xulofuranose
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6--
deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6-morphiliny-
l-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-ch-
lorophenylcarbamate)-6-deoxy-6-morphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-morphilin-
yl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-m-
ethoxyphenylcarbamate)-6-deoxy-6-morphilinyl-.alpha.-L-xylo-2-hexulofurano-
se
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-m-
orphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl--
4-(phenylcarbamate)-6-deoxy-6-morphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-morp-
hilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(-
p-tolylcarbamate)-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-mor-
pholinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4--
(p-nitrophenylcarbamate)-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofura-
nose
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-morphil-
iny-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-c-
hlorophenylcarbamate)-6-deoxy-6-morphilinyl-.alpha.-L-xylo-2-hexulofuranos-
e
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-morphilin-
yl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-me-
thoxyphenylcarbamate)-6-deoxy-6-morphilinyl-.alpha.-L-xylo-2-hexulofuranos-
e
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-mor-
philinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl--
4-(phenylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-pi-
peridinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-isopropylidene-1-O-dodecyl-
-4-(p-tolylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranos-
e
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6--
piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodec-
yl-4-(p-nitrophenylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexul-
ofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-pip-
eridinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4--
(p-chlorophenylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofur-
anose
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-piperi-
dinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p--
methoxyphenylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuran-
ose
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-pi-
peridinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl--
4-(phenylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-pip-
eridinyl-.alpha.-L-xylo-2-hexulofuranose)
2,3-O-Isopropylidene-1-O-heptyl--
4-(p-tolylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-pi-
peridinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl--
4-(p-nitrophenylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofu-
ranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6-hexa-
methyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-do-
decyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-hexamethyleneimino-.alpha.-L-x-
ylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-
-6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-h-
examethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-
-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-hexamethyleneimino-.alpha.-L-
-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)--
6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-hexa-
methyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-de-
cyl-4-(p-tolylcarbamate)-6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hex-
ulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-hexam-
ethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-hep-
tyl-4-(phenylcarbamate)-6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexu-
lofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-hexamethyl-
eneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-
-(p-methoxyphenylcarbamate)-6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2--
hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)--
6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-Q-dodecyl-4-(phenylcarbamate)-6-deoxy-6-ethylpyrro-
lidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-
-(p-chlorophenylcarbamate)-6-deoxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-he-
xulofuranose
2,3-O-Isopropylidene-0.1-O-dodecyl-4-(p-tolylcarbamate)-6-deo-
xy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-e-
thylpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O--
dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-ethylpyrrolidinyl-.alpha.-L-x-
ylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6--
deoxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy-6-ethy-
lpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dec-
yl-4-(p-tolylcarbamate)-6-deoxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexul-
ofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-de-
oxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-ethyl-
pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-hept-
yl-4-(phenylcarbamate)-6-deoxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexulo-
furanose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deo-
xy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-ethylpyrro-
lidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4--
(p-methoxyphenylcarbamate)-6-deoxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-he-
xulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6--
deoxy-6-ethylpyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6-ethylpiper-
idinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4--
(p-chlorophenylcarbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2-hexu-
lofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-ethylpiperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-
-dodecyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-
-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylca-
rbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-ethylpiperid-
inyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-c-
hlorophenylcarbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2-hexulofu-
ranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-ethyl-
piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-
-4-(p-methoxyphenylcarbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2--
hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-
-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-ethylpiperi-
dinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-
-chlorophenylcarbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2-hexulo-
furanose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-et-
hylpiperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-he-
ptyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xyl-
o-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbama-
te)-6-deoxy-6-ethylpiperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6-ethylmorph-
ilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4--
(p-chlorophenylcarbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2-hexu-
lofuranose
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-ethylmorphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-
-dodecyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-
-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylca-
rbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-ethylmorphil-
inyl-.alpha.-L-xylo-2-hexulofuranose
2,3,O-Isopropylidene-1-O-decyl-4-(p-c-
hlorophenylcarbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2-hexulofu-
ranose
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-ethyl-
morphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-
-4-(p-methoxyphenylcarbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2--
hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-
-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-ethylmorphi-
linyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-
-chlorophenylcarbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2-hexulo-
furanose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-et-
hylmorphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-he-
ptyl-4-(p-methoxyphenylcarbamate)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xyl-
o-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbama-
te)-6-deoxy-6-ethylmorphilinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-hexamethyl-
eneimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl--
4-(methylcarbamate)-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-piperidiny-
l-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-dodecyl-4-(meth-
ylcarbamate)-6-deoxy-6-(2-ethylpyrroldinyl)-.alpha.-L-xylo-2-hexulofuranos-
e
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-(2-ethylm-
orpholinyl)-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-
-4-(methylcarbamate)-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-hexamethylen-
eimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(m-
ethylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-(2-ethylpyrr-
olidinyl)-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-decyl-4-
-(methylcarbamate)-6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulof-
uranose
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-pyrr-
olidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-
-(methylcarbamate)-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-hexamethyle-
neimino-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4--
(methylcarbamate)-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-(2-ethylpyr-
rolidinyl)-.alpha.-L-xylo-2-hexulofuranose
2,3-O-Isopropylidene-1-O-heptyl-
-4-(methylcarbamate)-6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexul-
ofuranose.
4. A pharmaceutical composition comprising a pharmaceutically
effective amount of a compound as defined in claims 1, 0.2 or 3 and
a pharmaceutically acceptable carrier.
5. A process, according to claim 1, for preparing compounds of
Formula I: 10and their pharmaceutically acceptable salts, esters,
enantiomers, diastereomers, N-oxides, amides, prodrugs, metabolites
or polymorphs, wherein R is C.sub.1 to C.sub.1-5 alkyl, alkene,
alkyne (straight chain or branched), aryl, substituted aryl or
alkylaryl and R.sub.1 is phenyl o-, m- or p-chlorophenyl, tolyl,
methoxyphenyl or nitrophenyl and R.sub.2 is H, pyrrolidinyl,
piperidinyl, morpholinyl or hexamethyleneimino or a radical of the
formula NHR.sub.3, wherein R.sub.3 is C.sub.1 to C.sub.1-5 alkyl,
alkene or alkyne (straight chain or branched) or a radical of
Formula III: 11wherein n is a whole number up to 5 and 12is a
five-, six- or seven-membered heterocyclic ring containing one or
more heteroatoms, by treating the compound of Formula II with a
suitable isocyanate and in a suitable solvent at low temperature as
follows: 13
6. A process according to claim 5, wherein 14is pyrrolidinyl,
piperidinyl, morpholinyl or hexamethyleneimino.
7. The method of preventing, inhibiting or suppressing cell
adhesion in an animal comprising administering to said animal, a
compound having the structure of Formula I: 15and its
pharmaceutically acceptable salts, esters, enantiomers,
diastereomers, N-oxides, amides, prodrugs, metabolites, or
polymorphs, wherein R is C.sub.1 to C.sub.1-5 alkyl, alkene, alkyne
(straight chain or branched), aryl, substituted aryl or alkylaryl
and R.sub.1 is phenyl, o,- m- or p-chlorophenyl, tolyl,
methoxyphenyl or nitrophenyl and R.sub.2 is H, pyrrolidinyl,
piperidinyl, morphilinyl or hexamethyleneimino or a radical of the
formula NHR.sub.3, wherein R.sub.3 is C.sub.1 to C.sub.1-5 alkyl,
alkene or alkyne (straight chain or branched) or a radical of
Formula III: 16in which n is a whole number up to 5 and 17is a
five-, six- or seven-membered heterocyclic ring containing one or
more heteroatoms.
8. The method of claim 7, wherein 18is pyrrolidinyl, piperidinyl,
morpholinyl or hexamethyleneimino moieties.
9. A method for treating an animal suffering from bronchial asthma,
rheumatoid arthritis, multiple sclerosis, type I diabetes,
psoriasis, allograft rejection, and other inflammatory and/or
autoimmune disorders in an animal comprising administering to said
animal a compound of the structure of Formula I: 19wherein R is
C.sub.1 to C.sub.1-5 alkyl, alkene, alkyne (straight chain or
branched), aryl, substituted aryl or alkylaryl and R.sub.1 is
phenyl, o,- m- or p-chlorophenyl, tolyl, methoxyphenyl or
nitrophenyl and R.sub.2 is H, pyrrolidinyl, piperidinyl,
morphilinyl or hexamethyleneimino or a radical of formula
NHR.sub.3, wherein R.sub.3 is C.sub.1 to C.sub.1-5 alkyl, alkene or
alkyne (straight chain or branched) or a radical of Formula III:
20in which n is a whole number up to 5 and 21is a five-, six- or
seven-membered heterocyclic ring containing one or more
heteroatoms.
10. The method of claim 9, wherein 22is pyrrolidinyl, piperidinyl,
morpholinyl or hexamethyleneimino.
11. The method of preventing, inhibiting or suppressing cell
adhesion in an animal comprising the step of administering to said
animal the pharmaceutical composition according to claim 4.
12. The method according to claim 7 wherein said method is used for
preventing, inhibiting or suppressing cell adhesion-associated
inflammation.
13. The method-according to claim 7 wherein said method is used for
preventing, inhibiting or suppressing a cell adhesion-associated
immune or autoimmune response.
14. The method according to claim 7 or 9 wherein said method is
used to treat or prevent a disease selected from the group
consisting of asthma, arthritis, psoriasis, allograft rejection,
multiple sclerosis, diabetes and inflammatory bowel disease.
Description
FIELD OF THE INVENTION
[0001] This invention relates generally to compounds and processes
for synthesizing derivatives of
2-3-O-isopropylidene-.alpha.-L-xylo-2-hexulof- uranosonic acid. The
compounds of this invention are useful, inter-alia, for the
inhibition and prevention of cell adhesion and cell
adhesion-mediated pathologies, including inflammatory and
autoimmune diseases, such as bronchial asthma, rheumatoid
arthritis, type I diabetes, multiple sclerosis, allograft rejection
and psoriasis. This invention also relates to pharmacological
compositions containing derivatives of
2-3-O-isopropylidene-.alpha.-L-xylo-2-hexulofuranosonic acid and
the methods of treating such pathologies as listed above.
BACKGROUND OF THE INVENTION
[0002] Cell adhesion is a process by which cells associate with
each other and migrate towards a specific target localized within
the extracellular matrix. Specialized molecules, called cell
adhesion molecules (CAMs), mediate these reactions. CAMs have been
demonstrated to participate in various cell-cell,
cell-extracellular matrix, and platelet-platelet interactions. CAMs
influence the leukocytes' adhesion to the vascular endothelium,
their transendothelial migration, retention at extravascular sites,
and activation of T cells and eosinophils. These processes are
central to the pathogenesis of inflammatory and autoimmune
diseases. Therefore, CAMs are considered potential targets for
treating such disorders.
[0003] CAMs can be classified into three groups: integrins,
selectins, and the immunoglobulin superfamily. Of these, integrins
are the key mediators in the adhesive interactions between
hemopoietic cells and their microenvironment. They are comprised of
alpha-beta heterodimers and integrate signals from the outside to
the inside of cells, and vice versa. Integrins can be classified on
the basis of the beta subunits they contain. For example, the
beta-1 subfamily-contains beta-1 subunit noncovalently linked to
one of the 10 different alpha subunits.
[0004] The alpha-4 beta-1 integrin, also known as VLA.sub.4 (very
late activation antigen 4), is a member of the beta-1 integrin
family and comprises alpha-4 and beta-1 subunits. VLA.sub.4
interacts with two specific ligands--the vascular cell adhesion
molecule (VCAM-1) and the CS1 region of the protein fibronectin.
Adhesion mediated by VLA.sub.4 is central to the process of
transendothelial migration of leukocytes. Ligation of VLA.sub.4 is
followed by gross rearrangement of the cytoskeleton, leading to
flattening of cells along the blood vessel wall, followed by
expression of specific molecules that digest the endothelial cell
wall and diapedesis. Once in the extraluminal region, the
interactions of VLA.sub.4 with extracellular fibronectin play a
crucial role in the migration of leukocytes to the site of
inflammation, T cell proliferation, expression of cytokines and
inflammatory mediators. Additionally, VLA.sub.4 ligation provides
co-stimulatory signals to the leukocytes, resulting in enhanced
immunoreactivity. Thus, appropriate VLA.sub.4 antagonists would, in
theory, ameliorate the immune response through a twofold
action-inhibition of T cell recruitment at the site of inflammation
and inhibition of co-stimulatory activation of immune cells.
[0005] In this respect, inhibitors of VLA.sub.4 interactions have
been demonstrated to exhibit beneficial therapeutic effects in
several animal models of inflammatory and allergic diseases,
including sheep allergic asthma (Abraham et al, J. Clin. Invest.
1994;93:776); arthritis (Wahl et al, J. Clin. Invest. 1994;94:655);
experimental allergic encephalomyelitis (Yednock et al, Nature
(Lond), 1992;356:63 and Baron et al, J. Exp. Med. 1993;177:57).;
contact hypersensitivity (Chisolm et al, Eur J. Immunol.
1993;23:682); type I diabetes (Yang. et al, Proc. Natl. Acad. Sci.
(USA) 1993;90:10494); and inflammatory bowel disease. (Podolsky et
al, J. Clin. Invest. 1993;92:372).
[0006] The CS1 moiety region of fibronectin involved in the
interaction with VLA.sub.4 was identified as the tripeptide
Leu-Asp-Val (LDV) (Komoriya et al, J. Biol. Chem. 1991;266:15075).
Several peptides containing the LDV sequence were synthesized and
shown to inhibit the in vivo interaction of VLA.sub.4 to its
ligands (Ferguson et al, Proc. Natl. Acad. Sci. (USA) 1991;88:8072;
Wahl et al, J. Clin. Invest. 1994;94:655; Nowlin et al, J. Biol.
Chem. 1993;268(27):20352; and. PCT publication WO91/4862).
[0007] Despite these advances a need for small and specific
inhibitors of VLA.sub.4-dependent cell adhesion molecules remains.
Ideally, such inhibitors are water soluble with oral efficacy. Such
compounds would provide useful agents for the treatment, prevention
or suppression of various inflammatory pathologies mediated by
VLA.sub.4 binding.
[0008] It is generally known that isopropylidene and benzylidene
groups are the most commonly used protective groups in carbohydrate
chemistry. Although both groups are introduced into a molecule
under similar conditions, the location of the protection can be
quite different, and this difference is directly related to the
stability of each protected molecule. Since protection normally
occurs under conditions that allow reversibility, the reaction
proceeds until equilibrium is reached. The distribution of products
at equilibrium is determined by their relative thermodynamic
stabilities. In other words, these reactions are thermodynamically
controlled. Benzylidene groups prefer to be part of 6-membered ring
acetals, while the ketals resulting from acetonation generally are
5-membered rings. The difference is attributed to the effect of the
methyl and phenyl substituents on the stability of the particular
ring systems. These blocking methods are described in the U.S. Pat.
Nos. 2,715,121, 4,056,322, 4,735,934, 4,996,195 and 5,010,058, the
disclosures of which are incorporated herein by reference. Other
blocking methods are also described in J. Carbohydr. Chem.
1985;4:227 and 1984;3:331; Methods in Carbohydr. Chem. 1962;1:107
and 1962;1:191; Can J. Chem. 1984;62:2728, 1969;47:1195, 1455, and
1970;48:1754, all incorporated herein by reference. The prior art
reveals that D-glucose is blocked at the 1,2;5,6-positions with
either the isopropylidene or cyclohexylidene blocking group,
leaving the 3-position open to undergo derivatization. The
therapeutic activity of hexoses and their derivatives are also
disclosed in some of the above-cited prior art.
[0009] The compounds of the present invention were screened for
inhibitory activity in VLA.sub.4-mediated cell adhesion assay and
the classical murine hypersensitivity assay in mice. Several
compounds exhibited significant inhibitory activity in both tests.
The salts of these compounds could be easily solubilized in water
and used in the treatment of chronic, cell adhesion-mediated,
allergic, autoimmune and inflammatory disorders, such as bronchial
asthma and rheumatoid arthritis. Some of the prior art describes
development of peptide derivatives as cell adhesion antagonists for
treatment of these diseases. However, because treatment of chronic
diseases requires prolonged (mid-term to long-term) administration
of drugs, the development of specific, orally available cell
adhesion inhibitors would be very beneficial.
[0010] There is no example available in the prior art wherein the
compounds, containing a sugar nucleus coupled with carbamate
moiety, of the present invention are used as therapy for the
inhibition, prevention and suppression of VLA.sub.4-mediated cell
adhesion and pathologies associated with that adhesion.
SUMMARY OF THE INVENTION
[0011] An object of the present invention is to provide a process
for synthesizing a new class of compounds that exhibit significant
activity as VLA.sub.4 antagonists.
[0012] Most of the compounds described in U.S. Pat. No. 5,637,570
have shown significant anti-cancer activities and were devoid of
any anti-cell adhesion activities. Therefore, the compounds of the
present invention were designed and synthesized so as to enhance
their anti-cell adhesion properties. It was discovered that, for a
compound to be active as a cell adhesion inhibitor, it is best if
the sugar has a carbamate moiety along with other
functionalities.
[0013] It is a further object of this invention to provide a
process for the preparation of novel carbohydrate-based
water-soluble compounds that exhibit significant activity to be
used as cell adhesion antagonists.
[0014] Other objects and advantages of the present invention will
be set forth in the description that follows, will be in part
apparent from the description, or may be learned by the practice of
the invention. The objects and advantages of this invention may be
realized and obtained by means of the mechanisms and combinations
pointed out in the appended claims.
[0015] In order to achieve the above-mentioned objects and in
accordance with one aspect of the present invention, there is
provided a process for the synthesis of monosaccharide derivatives
and the derivatives themselves, having the structure of Formula I:
1
[0016] wherein R is C.sub.1 to C.sub.1-5 alkyl, alkene, alkyne
(straight chain or branched), aryl, substituted aryl or alkylaryl,
R.sub.1 is phenyl, o,- m- or p-chlorophenyl, tolyl, methoxyphenyl
or nitrophenyl and R.sub.2 is H, pyrrolidinyl, piperidinyl,
morphilinyl or hexamethyleneimino or a radical of the formula
--NHR.sub.3 wherein R.sub.3 is C.sub.1 to C.sub.1-5 alkyl, alkene
or alkyne (straight chain or branched) or a radical of Formula III:
2
[0017] wherein n is a whole number up to 5 and 3
[0018] is a five-, six- or seven-membered heterocyclic ring
containing one or more heteroatoms, and wherein preferably 4
[0019] is pyrrolidinyl, piperidinyl, morpholinyl or
hexamethyleneimino moieties. Preferred compounds are those wherein
R.sub.1 and R.sub.2 are not H at the same time. Acid addition salts
of the above compounds are also included in the invention.
[0020] In accordance with another aspect of the present invention
there is provided a list of compounds as shown below in the
description of the invention section.
[0021] In accordance with another aspect of the present invention
there are provided methods of preventing, inhibiting or suppressing
cell adhesion in an animal (the term animal as used herein includes
humans or mammals), comprising administering to said animal, the
compounds described above.
[0022] In accordance with another aspect of the present invention
there is provided a method for treating an animal suffering from
bronchial asthma, rheumatoid arthritis, multiple sclerosis, type I
diabetes, psoriasis, allograft rejection, and other inflammatory
and/or autoimmune disorders, comprising administering to said
animal, the compounds described above.
[0023] In accordance with yet another aspect of the present
invention there is provided a method for preventing, inhibiting or
suppressing cell adhesion-associated inflammation with compounds
described above.
[0024] In accordance with a further aspect of the present invention
there is provided a method for preventing, inhibiting or
suppressing a cell adhesion-associated immune or autoimmune
response with the compounds described above.
[0025] In accordance with another aspect of the present invention
there is provided a method for treating or preventing a disease
selected from the group consisting of asthma, arthritis, psoriasis,
allograft rejection, multiple sclerosis, diabetes and inflammatory
bowel disease, with the compounds as described above.
[0026] The compounds of the present invention are novel and exhibit
significant potency in terms of their activity, which was
determined by in vitro VLA.sub.4-mediated cell adhesion assay and
in vivo mouse ear swelling test. The compounds that were found
active in in vitro assay were tested in vivo. Some of the compounds
of the present invention were found to be potent VLA.sub.4
antagonists. Therefore, the present invention provides the
pharmaceutical compositions for the possible treatment of bronchial
asthma and other inflammatory and autoimmune disorders. In
addition, the compounds of the above invention can be administered
orally or parenterally.
DETAILED DESCRIPTION OF THE INVENTION
[0027] The compounds of the present invention may be prepared by
techniques well-known in the art and familiar to the average
synthetic organic chemist. In addition, the compounds of the
present invention may be prepared by the following novel and
inventive reaction sequence, which also show preferred R, R.sub.1
and R.sub.2 groups. 5
[0028] 2,3-O-Isopropyl-1-O-alkyl or
arylalkyl-6-deoxy-6-aminosubstituted-L- -xylo-2-hexulofuranose
compounds of Formula II, as shown in Scheme I, are prepared
according to the method described in U.S. Pat. No. 5,637,570 and
are the intermediates for the synthesis of the compounds of Formula
I of the present invention. Thus, the following intermediates were
prepared following the process as described in U.S. Pat. No.
5,637,570:
[0029]
2,3-O-isopropylidene-6-deoxy-6-hexamethyleneimino-1.-O-dodecyl-.alp-
ha.-L-xylo-2-hexulofuranose
[0030]
2,3-O-isopropylidene-6-deoxy-6-hexamethyleneimino-1-O-decyl-.alpha.-
-L-xylo-2-hexulofuranose
[0031]
2,3-O-isopropylidene-6-deoxy-6-hexamethyleneimino-1-O-heptyl-.alpha-
.-L-xylo-2-hexulofuranose
[0032]
2,3-O-isopropylidene-6-deoxy-6-pyrrolidinyl-1-O-dodecyl-.alpha.-L-x-
ylo-2-hexulofuranose
[0033]
2,3-O-isopropylidene-6-deoxy-6-pyrrolidinyl-1-O-decyl-.alpha.-L-xyl-
o-2-hexulofuranose
[0034]
2,3-O-isopropylidene-6-deoxy-6-pyrrolidinyl-1-O-heptyl-.alpha.-L-xy-
lo-2-hexulofuranose
[0035]
2,3-O-isopropylidene-6-deoxy-6-morphilinyl-1-O-dodecyl-.alpha.-L-xy-
lo-2-hexulofuranose
[0036]
2,3-O-isopropylidene-6-deoxy-6-morphilinyl-1-O-decyl-.alpha.-L-xylo-
-2-hexulofuranose
[0037]
2,3-O-isopropylidene-6-deoxy-6-morphilinyl-1-O-heptyl-.alpha.-L-xyl-
o-2-hexulofuranose
[0038]
2,3-O-isopropylidene-6-deoxy-6-piperidinyl-1-O-dodecyl-.alpha.-L-xy-
lo-2-hexulofuranose
[0039]
2,3-O-isopropylidene-6-deoxy-6-piperidinyl-1-O-decyl-.alpha.-L-xylo-
-2-hexulofuranose
[0040]
2,3-O-isopropylidene-6-deoxy-6-piperidinyl-1-O-heptyl-.alpha.-L-xyl-
o-2-hexulofuranose
[0041]
2,3-O-isopropylidene-6-deoxy-6-ethylpyrrolidinyl-1-O-dodecyl-.alpha-
.-L-xylo-2-hexulofuranose
[0042]
2,3-O-isopropylidene-6-deoxy-6-ethylpyrrolidinyl-1-O-decyl-.alpha.--
L-xylo-2-hexulofuranose
[0043]
2,3-O-isopropylidene-6-deoxy-6-ethylpyrrolidinyl-1-O-heptyl-.alpha.-
-L-xylo-2-hexulofuranose
[0044]
2,3-O-isopropylidene-6-deoxy-6-ethylmorpholinyl-1-O-dodecyl-.alpha.-
-L-xylo-2-hexulofuranose
[0045]
2,3-O-isopropylidene-6-deoxy-6-ethylmorpholinyl-1-O-decyl-.alpha.-L-
-xylo-2-hexulofuranose
[0046]
2,3-O-isopropylidene-6-deoxy-6-ethylmorpholinyl-1-O-heptyl-.alpha.--
L-xylo-2-hexulofuranose.
[0047] Thus, the compound of Formula II is treated with an
appropriate isocyanate in a suitable solvent at low temperature,
preferably at 0-10.degree. C. to afford the compounds of Formula I
of the present invention. An illustrative list of particular
compounds according to the invention and capable of being produced
by Scheme I include:
[0048] Compound Chemical Name
[0049] No.
[0050] 01.
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-py-
rrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0051] 02.
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbarhate)-6-deoxy-6-
-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0052] 03.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0053] 04.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0054] 05.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0055] 06.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0056] 07.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0057] 08.
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-py-
rrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0058] 09.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0059] 10.
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-p-
yrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0060] 11.
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-d-
eoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0061] 12.
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deo-
xy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0062] 13.
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-p-
yrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0063] 14.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0064] 15.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0065] 16.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-pyrrolidinyl-o-L-xylo-2-hexulofuranose
[0066] 17.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-de-
oxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0067] 18.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0068] 19.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0069] 20.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0070] 21.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0071] 22.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0072] 23.
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-mo-
rpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0073] 24.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0074] 25.
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-m-
orpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0075] 26.
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-d-
eoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0076] 27.
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deo-
xy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0077] 28.
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-m-
orpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0078] 29.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0079] 30.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0080] 31.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0081] 32.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-de-
oxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0082] 33.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0083] 34.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0084] 35.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0085] 36.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-piperidinyl-.alpha.-L-axylo-2-hexulofuranose
[0086] 37.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0087] 38.
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-pi-
peridinyl-.alpha.-L-xylo-2-hexulofuranose
[0088] 39.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0089] 40.
2,3-O-isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-p-
iperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0090] 41.
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-d-
eoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0091] 42.
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deo-
xy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0092] 43.
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-p-
iperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0093] 44.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0094] 45.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0095] 46.
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0096] 47.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-de-
oxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0097] 48.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0098] 49.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0099] 50.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0100] 51.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0101] 52.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0102] 53.
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-he-
xamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0103] 54.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0104] 55.
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-h-
examethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0105] 56.
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-d-
eoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0106] 57.
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deo-
xy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0107] 58.
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-h-
examethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0108] 59.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0109] 60.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0110] 61.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0111] 62.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-de-
oxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0112] 63.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0113] 64.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0114] 65.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0115] 66.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0116] 67.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0117] 68.
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-(2-
-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0118] 69.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0119] 70.
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-(-
2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0120] 71.
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-d-
eoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0121] 72.
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deo-
xy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0122] 73.
2,3-O-isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-(-
2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0123] 74.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0124] 75.
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0125] 76.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0126] 77.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-de-
oxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0127] 78.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0128] 79.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0129] 80.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0130] 81.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0131] 82.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0132] 83.
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-(2-
-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0133] 84.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0134] 85.
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-(-
2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0135] 86.
2,3O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-de-
oxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0136] 87.
2,3-O-Isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deo-
xy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0137] 88.
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6-(-
2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0138] 89.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-d-
eoxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0139] 90.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6--
(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0140] 91.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0141] 92.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-de-
oxy-6-(2-ethylpiperidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0142] 93.
2,3-O-Isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-6-deoxy-6--
(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0143] 94.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0144] 95.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-
-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0145] 96.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0146] 97.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0147] 98.
2,3-O-Isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-deoxy-6-(2-
-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0148] 99.
2,3-O-Isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-de-
oxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0149] 100.
2,3-O-Isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6--
(2-ethylmorphilinyl)-c-L-xylo-2-hexulofuranose
[0150] 101.
2,3-O-Isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6--
deoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0151] 102.
2,3-O-Isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6--
deoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0152] 103.
2,3-O-Isopropylidene-1-O-heptyl-4-(phenylcarbamate)-6-deoxy-6--
(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0153] 104.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6--
deoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0154] 105.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-
-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0155] 106.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-
-deoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0156] 107.
2,3-O-Isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-d-
eoxy-6-(2-ethylmorphilinyl)-.alpha.-L-xylo-2-hexulofuranose
[0157] 108.
2,3-O-Isopropylidene-1-O-dodecyl-4-.(methylcarbamate)-6-deoxy--
6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0158] 109.
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-
-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0159] 110.
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-
-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0160] 111.
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-
-(2-ethylpyrroldinyl)-.alpha.-L-xylo-2-hexulofuranose
[0161] 112.
2,3-O-Isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-
-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0162] 113.
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-m-
orpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0163] 114.
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-h-
examethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0164] 115.
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-p-
iperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0165] 116.
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-(-
2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0166] 117.
2,3-O-Isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-(-
2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0167] 118.
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6--
pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0168] 119.
2,3-O-Isopropylidene-1-O-heptyl-4-.(methylcarbamate)-6-deoxy-6-
-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0169] 120.
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6--
hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0170] 121.
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6--
piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0171] 122.
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6--
(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0172] 123.
2,3-O-Isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6--
(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0173] The sugar derivatives of the present invention exhibit
various pharmacological properties and are useful for treating
animals, the term animal as defined herein includes human or
mammal, with various inflammatory and autoimmune disorders, such as
bronchial asthma, rheumatoid arthritis, type I diabetes, multiple
sclerosis, allograft rejection and psoriasis.
[0174] The free amino compounds of the present invention are basic
and form organic and inorganic acid salts. The resulting salts are
useful by themselves and in the therapeutic composition and method
of use. These salts may be prepared by the usual prior art
techniques, such as suspending the compound in water and then
adding one equivalent of the desired organic or mineral acid.
Examples of preferred acids include hydrochloric, sulphuric,
nitric, maleic, benzoic, tartaric, acetic, p-aminobenzoic, oxalic,
succinic and glucoronic acid.
[0175] The neutral solution of the resulting salt is subjected to
rotary evaporation under diminished pressure to the volume
necessary to ensure precipitation of the salt upon cooling, which
is then filtered and dried. The salts of the present invention may
also be prepared strictly under non-aqueous conditions. For
example, dissolving the free amine in a suitable organic solvent,
adding exactly one equivalent of the desired acid to the same
solvent and stirring the solution at 0-5.degree. C. causes
precipitation of the amine salt, which is then filtered, washed
with solvent and dried. The amine salts are often preferred for use
in formulating the therapeutic compositions as they are crystalline
and relatively more stable and non-hydroscopic. The amine salts are
also better adapted for intramuscular injection than are the free
amines.
[0176] Because of their valuable pharmacological properties, the
compounds of the present invention may be administered to an animal
for treatment orally, topically, rectally, internasally or by
parenteral route. When the therapeutic composition is to be
administered orally, it is preferred that the compounds of the
present invention are admixed with a filler and/or binder, such as
starch and a disintegrator. The admixture may be pressed into a
tablet conveniently sized for oral administration. Capsules may
also be filled with the powdered therapeutic composition for oral
administration. Alternatively, a water solution of the amine salt
or suspension of the therapeutic composition may be admixed with a
flavored syrup and administered orally. A salt of the free acid is
usually preferred when the compound is administered by parenteral
route.
[0177] The pharmaceutical compositions of the present invention are
preferably produced and administered in dosage units, with each
unit containing a certain amount of at least one compound of the
invention and/or at least one physiologically acceptable base salt
addition thereof. The dosage may be varied over extremely wide
limits, as the compounds are effective at low dosage levels and
relatively free of toxicity. The compounds may be administered in
the low micromolar concentration, which is therapeutically
effective, and the dosage may be increased as desired up to the
maximum dosage tolerated by the patient.
[0178] The present invention also includes within its scope
prodrugs of the compounds of Formula I. In general, such prodrugs
will be functional derivatives of these compounds which are readily
converted in vivo into the defined compounds. Conventional
procedures for the selection and preparation of suitable prodrugs
are known.
[0179] The present invention also includes the enantiomers,
diastereomers, N-oxides, polymorphs and pharmaceutically acceptable
salts of these compounds as well as metabolites having the same
type of activity. This invention further includes pharmaceutical
compositions comprising the molecules of Formula I or prodrugs,
metabolite enantiomers, diastereomers, N-oxides, polymorphs or
pharmaceutically acceptable salts thereof, in combination with
pharmaceutically acceptable carriers and optionally included
excipients.
[0180] The examples mentioned below demonstrate the general
synthetic procedure as well as the specific preparation of the
preferred compounds. The examples are provided to illustrate the
details of the invention and should not be considered to limit the
scope of the present invention.
Experimental Details
[0181] Various solvents, such as acetone, methanol, pyridine,
ether, tetrahydrofuran, hexane and dichloromethane, were dried
using various drying agents according to the procedure described in
the literature. Wet solvents gave poor yields of the products and
intermediates. IR spectra were recorded as nujol mulls or a thin
neat film on a Perkin Elmer Paragon instrument. Nuclear Magnetic
Resonance (NMR) data (H, C) were recorded using a Varian XL-300 MHz
instrument using tetramethylsilane as an internal standard.
Chemical Ionization Mass Spectra (CIMS) were obtained using a
Finnigan MAT-4510 mass spectrometer equipped with an INCOS data
system. Generally, a direct exposure probe and methane as the
reagent gas (0.33 mmHg, 120.degree. C. source temperature) were
used.
EXAMPLE 1
[0182] Preparation of
2,3-O-isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-
-6-deoxy-6-hexa-methyleneimino-.alpha.-L-xylo-2-hexulofuranose.
[0183]
2,3-O-Isopropylidene-1-O-dodecyl-6-deoxy-6-hexamethyleneimino-.alph-
a.-L-xylo-2-hexulofuranose (prepared according to the method
described in U.S. Pat. No. 5,637,570) (2.0 gm) was dissolved in dry
methylene chloride (20 ml). To this solution was added phenyl
isocyanate (0.64 gm) dropwise at 0-10.degree. C. and the reaction
mixture was stirred at the same temperature for 2 hours. It was
then washed with water (2 times 5 ml) and brine (2 times 5 ml). The
organic layer was dried and the solvent was removed. The crude
product so obtained was purified by column chromatography and
eluted with 50% ethylacetate in hexane. Pure product yield:
61%.
[0184] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-hexamethyleneimino-.alpha.-L-x-
ylo-2-hexulofuranose with a suitable isocyanate:
[0185]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0186]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-hex-
amethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0187]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0188]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0189]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-hexa-
methyleneimino-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 2
[0190] Preparation of
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6- -d
oxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose.
[0191]
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-pyrrolidinyl-.alpha.-L-x-
ylo-2-hexulofuranose (prepared as described in Example 1 by
replacing the hexamethyleneimino group with pyrrolidine at position
6) (1.9 gm) was dissolved in methylene chloride (20 ml). To this
solution was added phenyl isocyanate (0.56 gm) dropwise at
0-10.degree. C. and the reaction mixture was stirred at the same
temperature for 2 hours. The organic layer was washed with water (2
times 10 ml), followed by saturated solution of sodium chloride (2
times 10 ml), dried over anhydrous sodium sulfate and filtered. The
solvent was removed with rotary evaporation. The crude product so
obtained was purified by flash chromatography using silica gel and
eluted with 30% ethylacetate in hexane. Pure product yield: 53.80%
(1.0 gm).
[0192] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2--
hexulofuranose with a suitable isocyanate:
[0193]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0194]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-pyr-
rolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0195]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0196]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0197]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-pyrr-
olidinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 3
[0198] Preparation of
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose.
[0199]
2,3-O-Isopropylidene-1-O-dodecyl-6-deoxy-6-morpholinyl-.alpha.-L-xy-
lo-2-hexulofuranose (prepared as described in Example 1 by
replacing the hexamethyleneimino group with the morpholine group at
position 6) (2.0 gm) was dissolved in methylene chloride (20 ml).
To this solution was added phenyl isocyanate (1.0 ml) dropwise at
0-10.degree. C. and the reaction mixture was stirred at the same
temperature for 2 hours. The organic-layer was washed with water (2
times 10 ml), followed by saturated solution of sodium chloride (2
times 10 ml), dried over anhydrous sodium sulfate and filtered. The
solvent was removed with rotary evaporation. The crude product so
obtained was purified by flash chromatography using silica gel and
eluted with 30% ethylacetate in hexane. Pure product yield: 54.6%
(1.20 gm).
[0200] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-h-
exulofuranose with a suitable isocyanate:
[0201]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0202]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-mor-
pholinyl-.alpha.-L-xylo-2-hexulofuranose
[0203]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0204]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0205]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-morp-
holinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 4
[0206] Preparation of
2,3-O-isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-
-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose.
[0207]
2,3-O-Isopropylidene-1-O-dodecyl-6-deoxy-6-morpholinyl-.alpha.-L-xy-
lo-2-hexulofuranose (prepared as described in Example 1 by
replacing the hexamethyleneimino group with the piperidino group at
position 6) (2.0 gm) was dissolved in methylene chloride (20 ml).
To this solution was added phenyl isocyanate (0.58 gm) dropwise at
0-10.degree. C. and the reaction mixture was stirred at the same
temperature for 2 hours. The reaction was monitored with thin layer
chromatography (TLC). The organic layer was washed with water (2
times 10 ml), followed by saturated solution of sodium chloride (2
times 10 ml), dried over anhydrous sodium sulfate and filtered. The
solvent was removed with rotary evaporation. The crude product so
obtained was purified by flash chromatography using silica gel and
eluted with 30% ethylacetate in hexane. Pure product yield: 35.1%
(0.90 gm).
[0208] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-h-
exulofuranose with a suitable isocyanate:
[0209]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0210]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-pip-
eridinol-.alpha.-L-xylo-2-hexulofuranose
[0211]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0212]
2,3-O-isopropylidene-1-o-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0213]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-pipe-
ridinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 5
[0214] Pr paration of
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0215]
2,3-O-Isopropylidene-1-O-dodecyl-6-deoxy-6-(2-ethylpyrrolidinyl)-.a-
lpha.-L-xylo-2-hexulofuranose (prepared as described in Example 1
by replacing the hexamethyleneimino group with the
2-ethylpyrrolidinyl group at position 6) (1.5 gm) was dissolved in
methylene chloride (20 ml). To this solution was added phenyl
isocyanate (1.0 ml) dropwise at 0-10.degree. C. and the reaction
mixture was stirred at the same temperature for 2 hours. The
reaction was monitored with TLC. The organic layer was washed with
water (2 times 10 ml), followed by saturated solution of sodium
chloride (2 times 10 ml), dried over anhydrous sodium sulfate and
filtered. The solvent was removed with rotary evaporation. The
crude product so obtained was purified by flash chromatography
using silica gel and eluted with 30% ethylacetate in hexane. Pure
product yield: 60.2% (1.1 gm).
[0216] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.--
L-xylo-2-hexulofuranose with a suitable isocyanate:
[0217]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0218]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-(2--
ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0219]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0220]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0221]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-(2-e-
thylpyrroldinyl)-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 6
[0222] Preparation of
2,3,O-isopropylidene-1-O-dodecyl-4-(phenylcarbamate)-
-6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0223]
2,3-O-Isopropylidene-1-O-dodecyl-6-deoxy-6-(2-ethylmorpholinyl)-.al-
pha.-L-xylo-2-hexulofuranose (prepared as described in Example 1 by
replacing the hexamethyleneimino group with the 2-ethylmorpholino
group at position 6) (2.0 gm) was dissolved in methylene chloride
(20 ml). To this solution was added phenyl isocyanate (0.56 gm)
dropwise at 0-10.degree. C. and the reaction mixture was stirred at
the same temperature for 2 hours. The reaction was monitored with
TLC. The organic layer was washed with water (2 times 10 ml),
followed by saturated solution of sodium chloride (2 times 10 ml),
dried over anhydrous sodium sulfate and filtered. The solvent was
removed with rotary evaporation. The crude product so obtained was
purified by flash chromatography using silica gel and eluted with
30% ethylacetate in hexane. Pure product yield: 30.4% (0.75
gm).
[0224] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-dodecyl-6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-
-xylo-2-hexulofuranose with a suitable isocyanate:
[0225]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0226]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-(2--
ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0227]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0228]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0229]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-(2-e-
thylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 7
[0230] Preparation of
2,3,0-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose.
[0231] This compound was prepared according to method described in
Example 2 by reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-pyrrolidinyl-.alph-
a.-L-xylo-2-hexulofuranose with phenyl isocyanate at 0-10.degree.
C. Pure product yield: 58%.
[0232] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-he-
xulofuranose with the desired isocyanate:
[0233]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-chlorophenylcarbamate)-6-deox-
y-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0234]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-tolylcarbamate)-6-deoxy-6-pyr-
rolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0235]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-methoxyphenylcarbamate)-6-deo-
xy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0236]
2,3-O-isopropylidene-1-O-dodecyl-4-(p-nitrophenylcarbamate)-6-deoxy-
-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0237]
2,3-O-isopropylidene-1-O-dodecyl-4-(methylcarbamate)-6-deoxy-6-pyrr-
olidinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 8
[0238] Preparation of
2,3,O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose.
[0239] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-morpholiny-
l-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate at
0-10.degree. C. Pure product yield: 61%.
[0240] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hex-
ulofuranose with the desired isocyanate:
[0241]
2,3-O-isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy--
6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0242]
2,3-O-isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-morph-
olinyl-.alpha.-L-xylo-2-hexulofuranose
[0243]
2,3-O-isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-
-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0244]
2,3-O-isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-
-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0245]
2,3-O-isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-morpho-
linyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 9
[0246] Preparation of
2,3-O-isopropylldene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose.
[0247] This compound was prepared according to the method described
in Example 1 by reacting 2,3-O-isopropylidene-1-O-decyl-6-deoxy-6
examethyleneimino-.alpha.-L-xylo-2-hexulofuranose with phenyl
isocyanate at 0-10.degree. C. Pure product yield: 69%.
[0248] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-hexamethyleneimino-.alpha.-L-xyl-
o-2-hexulofuranose with the desired isocyanate:
[0249]
2,3-O-isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy--
6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0250]
2,3-O-isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-hexam-
ethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0251]
2,3-O-isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-
-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0252]
2,3-O-isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-
-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0253]
2,3-O-isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-hexame-
thyleneimino-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 10
[0254] Preparation of
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose.
[0255] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-piperidiny-
l-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate at
0-10.degree. C. Pure product yield: 74%.
[0256] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hex-
ulofuranose with the desired isocyanate:
[0257]
2,3-O-isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy--
6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0258]
2,3-O-isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-piper-
idinyl-.alpha.-L-xylo-2-hexulofuranose
[0259]
2,3-O-isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-
-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0260]
2,3-O-isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-
-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0261]
2,3-O-isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-piperi-
dinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 11
[0262] Preparation of
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0263] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopro-pylidene-1-O-decyl-6-deoxy-6-(2-ethylp-
yrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate
at 0-10.degree. C. Pure product yield: 74%.
[0264] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L--
xylo-2-hexulofuranose with the desired isocyanate:
[0265]
2,3-O-isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy--
6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0266]
2,3-O-isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-(2-et-
hylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0267]
2,3-O-isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-
-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0268]
2,3-O-isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-
-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0269]
2,3-O-isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-(2-eth-
ylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 12
[0270] Preparation of
2,3-O-isopropylidene-1-O-decyl-4-(phenylcarbamate)-6-
-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0271] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-(2-ethylmo-
rpholinyl)-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate
at 0-10.degree. C. Pure product yield: 72%.
[0272] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-x-
ylo-2-hexulofuranose with the desired isocyanate:
[0273]
2,3-O-isopropylidene-1-O-decyl-4-(p-chlorophenylcarbamate)-6-deoxy--
6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0274]
2,3-O-isopropylidene-1-O-decyl-4-(p-tolylcarbamate)-6-deoxy-6-(2-et-
hylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0275]
2,3-O-isopropylidene-1-O-decyl-4-(p-methoxyphenylcarbamate)-6-deoxy-
-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0276]
2,3-O-isopropylidene-1-O-decyl-4-(p-nitrophenylcarbamate)-6-deoxy-6-
-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0277]
2,3-O-isopropylidene-1-O-decyl-4-(methylcarbamate)-6-deoxy-6-(2-eth-
ylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 13
[0278] Preparation of
2,3-O-isopropylidene-1-O-heptyl-4-(phenylcarbamate)-- 6-d
oxy-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose.
[0279] This compound was prepared according to the method described
in Example 2 by reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-pyrrolidi-
nyl-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate at
0-10.degree. C. Pure product yield: 85.4%
[0280] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-pyrrolidinyl-.alpha.-L-xylo-2-h-
exulofuranose with the desired isocyanate:
[0281]
2,3-O-isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-
-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0282]
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-pyrr-
olidinyl-.alpha.-L-xylo-2-hexulofuranose
[0283]
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deox-
y-6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0284]
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy--
6-pyrrolidinyl-.alpha.-L-xylo-2-hexulofuranose
[0285]
2,3-O-isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-pyrro-
lidinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 14
[0286] Preparation of
2,3-O-isopropylidene-1-O-heptyl-4-(phenylcarbamate)--
6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose.
[0287] This compound was prepared according to the method described
in. Example 3 by reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-morpholin-
yl-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate at
0-10.degree. C. Pure product yield: 79%.
[0288] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-decyl-6-deoxy-6-morpholinyl-.alpha.-L-xylo-2-hex-
ulofuranose with the desired isocyanate:
[0289]
2,3-O-isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-
-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0290]
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-morp-
holinyl-.alpha.-L-xylo-2-hexulofuranose
[0291]
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deox-
y-6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0292]
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy--
6-morpholinyl-.alpha.-L-xylo-2-hexulofuranose
[0293]
2,3-O-isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-morph-
olinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 15
[0294] Preparation of
2,3-O-isopropylidene-1-O-heptyl-4-(phenylcarbamate)--
6-deoxy-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose.
[0295] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-hexamethy-
lene-imino-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate
at 0-100 C. Pure product yield: 91%.
[0296] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-hexamethyleneimino-.alpha.-L-xy-
lo-2-hexulofuranose with the desired isocyanate:
[0297]
2,3-O-isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-
-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0298]
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-hexa-
methyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0299]
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deox-
y-6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0300]
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy--
6-hexamethyleneimino-.alpha.-L-xylo-2-hexulofuranose
[0301]
2,3-O-isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-hexam-
ethyleneimino-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 16
[0302] Preparation of 2,3-O-isopropylidene-1-O-h
ptyl-4-(phenylcarbamate)--
6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose.
[0303] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-piperidin-
yl-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate at
0-10.degree. C. Pure product yield: 47.6%.
[0304] The following compounds were synthesized similarly
by-reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-piperidinyl-.alpha.-L-xylo-2-he-
xulofuranose with the desired isocyanate:
[0305]
2,3-O-isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-
-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0306]
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-pipe-
ridinyl-.alpha.-L-xylo-2-hexulofuranose
[0307]
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deox-
y-6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0308]
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy--
6-piperidinyl-.alpha.-L-xylo-2-hexulofuranose
[0309]
2,3-O-isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-piper-
idinyl-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 17
[0310] Preparation of
2,3-O-isopropylidene-1-O-heptyl-4-(phenylcarbamate)--
6-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0311] This compound was prepared according to the method described
in Example 3 by reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-(2-ethylp-
yrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose with phenyl isocyanate
at 0-10.degree. C. Pure product yield: 68%.
[0312] The following compounds were synthesized similarly by
reacting
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-(2-ethylpyrrolidinyl)-.alpha.-L-
-xylo-2-hexulofuranose with the desired isocyanate:
[0313]
2,3-O-isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-
-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0314]
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-(2-e-
thylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0315]
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deox-
y-6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0316]
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy--
6-(2-ethylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose
[0317]
2,3-O-isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-(2-et-
hylpyrrolidinyl)-.alpha.-L-xylo-2-hexulofuranose.
EXAMPLE 18
[0318] Preparation of
2,3-O-isopropylidene-1-O-heptyl-4-(phenylcarbamate)--
6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0319] This compound was prepared similarly according to the method
described in Example 3 by reacting
2,3-O-isopropylidene.-1-O-heptyl-6-deo-
xy-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose with
phenyl isocyanate at 0-10.degree. C. Pure product yield: 75.8%.
[0320] The following compounds were synthesized similarly by
reacting the
2,3-O-isopropylidene-1-O-heptyl-6-deoxy-6-(2-ethylmorpholinyl)-.alpha.-L--
xylo-2-hexulofuranose with the desired isocyanate:
[0321]
2,3-O-isopropylidene-1-O-heptyl-4-(p-chlorophenylcarbamate)-6-deoxy-
-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0322]
2,3-O-isopropylidene-1-O-heptyl-4-(p-tolylcarbamate)-6-deoxy-6-(2-e-
thylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0323]
2,3-O-isopropylidene-1-O-heptyl-4-(p-methoxyphenylcarbamate)-6-deox-
y-6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0324]
2,3-O-isopropylidene-1-O-heptyl-4-(p-nitrophenylcarbamate)-6-deoxy--
6-(2-ethylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose
[0325]
2,3-O-isopropylidene-1-O-heptyl-4-(methylcarbamate)-6-deoxy-6-(2-et-
hylmorpholinyl)-.alpha.-L-xylo-2-hexulofuranose.
[0326] While the present invention has been described in terms of
its specific embodiments, certain modifications and equivalents
will be apparent to those skilled in the art and are intended to be
included within the scope of this invention, which is to be limited
only by the scope of the appended claims.
* * * * *