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"A Process For The Preparation Of Derivatives Of Monosaccharides As Novel Cell Adhesion Inhibitors"

Abstract: The present invention relates to a process for the preparation of derivatives of monosaccharides as novel Cell Adhesion Inhibitors and are useful for 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 and psoriasis.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
04 September 2002
Publication Number
1/2005
Publication Type
INA
Invention Field
PHARMACEUTICALS
Status
Email
Parent Application

Applicants

RANBAXY LABORATORIES LIMITED
1956 HEAD, OFFICE AT 12TH, FLOOR, DEVIKA TOWER, 6, NEHRU PLACE, NEW DELHI-110019, INDIA.

Inventors

1. SUDERSHAN KUMAR ARORA
RANBAXY LABORATORIES LIMITED, A-1, PHASE-I, OKHLA INDUSTRIAL AREA, NEW DELHI-110020, INDIA.
2. MADAN PAL TANWAR
DEXTER CHEMICALS (I) PVT. LTD, MATHANA CHOWKI, LADWA ROAD, MATHANA, KURUKSHETRA (HARYANA), INDIA.
3. JANG BAHADUR GUPTA
RANBAXY LABORATORIES LIMITED, A-1, PHASE-I, OKHLA INDUSTRIAL AREA, NEW DELHI-110020, INDIA.
4. GEETA SHARMA
RANBAXY LABORATORIES LIMITED, A-1, PHASE-I, OKHLA INDUSTRIAL AREA, NEW DELHI-110020, INDIA.

Specification

We Claim:
1. A process for preparation of derivatives of monosaccharides as novel cell adhesion inhibitors of Formula II (as shown in the accompanied drawings) which consists of epimannofuranoside or lyxofuranoside derivatives and it's pharmaceutically acceptable salts, wherein
R is C1-C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or aralkyl;
R' is SO2C6H5, SO2C6H4CH3-p or SO2C6H4CI-p, phenyl or substituted phenyl represented as C6H4 R"'-p, wherein R'" is Cl, NO2, OCH3, CH3, CH2COOH, CH2COOCH3, CH2COLDVP, CH2CODVP, CH2COVP wherein LDVP, DVP and VP represent tetrapeptide (Leucyl aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl) respectively, R" is H or CH3 and (wwww) represents epiglucofuranose, epiallofuranose, xylofuranose or ribofuranose configuration thereof which comprises reacting 2,3-O-isopropylidene-6-deoxy-1-O-alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl, substituted aryl or alkylaryl mannofuranoside of Formula XI (as shown in the accompanied drawings) wherein R has the same meaning as defined above and R" is CH3 with p-toluene sulfonyl chloride in an organic base selected from the group consisting of pyridine, N-methylmorpholine or diisopropylethylamine and cooled the reaction mixture at a temperature ranging from 0 to 15°C followed by the reaction with sodium azide in an organic solvent selected from the group consisting of dimethylformamide, tetrahydrofuran, diethylether or dioxane and heated the reaction mixture at temperature ranging form 50 to 140°C, which is reduced with lithium aluminium hydride in an organic solvent selected from the group consisting of tetrahydrofuran, dimethylformamide, dioxane or diethylether to afford the corresponding 5-deoxy-5-amino epimannofuranoside derivatives of Formula XII (as shown in the accompanied drawings) wherein R and R" have the same meanings as defined above, which are treated with the isocyanates R'NCO (wherein R' SO2C6H5, SO2C6H4CH3-p or SO2C6H4CI-p, C6H4CH2-COOCH3) C6H4CH2COOH, C6H4R"-p and R" is Cl, NO2, OCH3, CH3, CH2COOH, CH2COOCH3, CH2COLDVP, CH2CODVP, CH2COVP, wherein LDVP, DVP and VP represent tetrapeptide (Leucyl-

aspartyl-valyl-propyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-propyl) respectively) in an organic solvent selected from the group consisting of methylene chloride, ethylene chloride, chloroform or carbon tetrachloride at a temperature ranging form -10 to 10° to give the compound of Formula II wherein R and R' have the same meanings defined earlier and R" is CH3.
2. The process for preparation of derivatives of monosaccharides of the compound of Formula II, substantially as herein described and illustrated by the examples herein.

We Claim:
1. A process for preparation of derivatives of monosaccharides as novel cell adhesion inhibitors of Formula II (as shown in the accompanied drawings) which consists of epimannofuranoside or lyxofuranoside derivatives and it's pharmaceutically acceptable salts, wherein
R is C1-C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or aralkyl;
R' is SO2C6H5, SO2C6H4CH3-p or SO2C6H4CI-p, phenyl or substituted phenyl represented as C6H4 R"'-p, wherein R'" is Cl, NO2, OCH3, CH3, CH2COOH, CH2COOCH3, CH2COLDVP, CH2CODVP, CH2COVP wherein LDVP, DVP and VP represent tetrapeptide (Leucyl aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl) respectively, R" is H or CH3 and (wwww) represents epiglucofuranose, epiallofuranose, xylofuranose or ribofuranose configuration thereof which comprises reacting 2,3-O-isopropylidene-6-deoxy-1-O-alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl, substituted aryl or alkylaryl mannofuranoside of Formula XI (as shown in the accompanied drawings) wherein R has the same meaning as defined above and R" is CH3 with p-toluene sulfonyl chloride in an organic base selected from the group consisting of pyridine, N-methylmorpholine or diisopropylethylamine and cooled the reaction mixture at a temperature ranging from 0 to 15°C followed by the reaction with sodium azide in an organic solvent selected from the group consisting of dimethylformamide, tetrahydrofuran, diethylether or dioxane and heated the reaction mixture at temperature ranging form 50 to 140°C, which is reduced with lithium aluminium hydride in an organic solvent selected from the group consisting of tetrahydrofuran, dimethylformamide, dioxane or diethylether to afford the corresponding 5-deoxy-5-amino epimannofuranoside derivatives of Formula XII (as shown in the accompanied drawings) wherein R and R" have the same meanings as defined above, which are treated with the isocyanates R'NCO (wherein R' SO2C6H5, SO2C6H4CH3-p or SO2C6H4CI-p, C6H4CH2-COOCH3) C6H4CH2COOH, C6H4R"-p and R" is Cl, NO2, OCH3, CH3, CH2COOH, CH2COOCH3, CH2COLDVP, CH2CODVP, CH2COVP, wherein LDVP, DVP and VP represent tetrapeptide (Leucyl-

aspartyl-valyl-propyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-propyl) respectively) in an organic solvent selected from the group consisting of methylene chloride, ethylene chloride, chloroform or carbon tetrachloride at a temperature ranging form -10 to 10° to give the compound of Formula II wherein R and R' have the same meanings defined earlier and R" is CH3.
2. The process for preparation of derivatives of monosaccharides of the compound of Formula II, substantially as herein described and illustrated by the examples herein.

Documents

Application Documents

# Name Date
1 900-del-2002-abstract.pdf 2011-08-20
1 900-del-2002-petition-138.pdf 2011-08-20
2 900-del-2002-pct-210.pdf 2011-08-20
2 900-del-2002-claims.pdf 2011-08-20
3 900-del-2002-form-4.pdf 2011-08-20
3 900-del-2002-correspondence-others.pdf 2011-08-20
4 900-del-2002-form-3.pdf 2011-08-20
4 900-del-2002-correspondence-po.pdf 2011-08-20
5 900-del-2002-description (complete).pdf 2011-08-20
5 900-del-2002-form-2.pdf 2011-08-20
6 900-del-2002-drawings.pdf 2011-08-20
6 900-del-2002-form-1.pdf 2011-08-20
7 900-del-2002-drawings.pdf 2011-08-20
7 900-del-2002-form-1.pdf 2011-08-20
8 900-del-2002-description (complete).pdf 2011-08-20
8 900-del-2002-form-2.pdf 2011-08-20
9 900-del-2002-correspondence-po.pdf 2011-08-20
9 900-del-2002-form-3.pdf 2011-08-20
10 900-del-2002-form-4.pdf 2011-08-20
10 900-del-2002-correspondence-others.pdf 2011-08-20
11 900-del-2002-pct-210.pdf 2011-08-20
11 900-del-2002-claims.pdf 2011-08-20
12 900-del-2002-petition-138.pdf 2011-08-20
12 900-del-2002-abstract.pdf 2011-08-20