Anti-Thrombotic Compounds

Abstract

New compounds, namely, (7aS,2′S)-2-oxoclopidogrel and its pharmaceutically acceptable salts thereof are disclosed for treatment or prophylaxis of thrombo-embolism and/or cardiovascular diseases.

We claim: 
     
         1 . A substantially pure compound of Formula IIA, or salts thereof, wherein the asterisks denote chiral carbon center centers having a (S,S) absolute stereochemical configuration: 
       
         
           
           
               
               
           
         
       
       wherein the compound is isolated substantially free from its isomers of Formulas IIB, VI and VII, wherein the asterisks in Formula IIB denote chiral carbon centers: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1 , wherein the isomers of Formula IIB, VI or VII are individually or cumulatively less than 10% by weight of the total compound. 
     
     
         3 . The compound of  claim 1 , wherein the isomers of Formula IIB, VI or VII are individually or cumulatively less than 3% by weight of the total compound. 
     
     
         4 . The compound of  claim 2 , wherein the isomers of Formula IIB, VI or VII are less than 2.0% by weight of the total compound. 
     
     
         5 . The compound of  claim 1 , wherein the salt is selected from the group consisting of hydrogen sulfate, methane sulfonate and benzene sulfonate. 
     
     
         6 . A substantially crystalline compound of  claim 1 . 
     
     
         7 . A pharmaceutical composition comprising the compound of  claim 1  and one or more pharmaceutically acceptable excipients. 
     
     
         8 . A pharmaceutical composition comprising a compound according to  claim 6 . 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the composition further comprises one or more active compounds selected from the group consisting of aspirin, statins, cilostazol, and dipyridamole. 
     
     
         10 . An isolated methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno [3,2-c]-5-pyridin-2-one)acetate or its salts or solvates; substantially free from isomers of Formulas IIB, VI and VII, wherein the asterisks in Formula IIB denote chiral carbon centers: 
       
         
           
           
               
               
           
         
       
     
     
         11 . Methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate hydrogen sulfate. 
     
     
         13 . Methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate methane sulfonate. 
     
     
         14 . Methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate benzene sulfonate. 
     
     
         15 . A pharmaceutical, composition comprising compound according to claim  12 ,  claim 13  or  claim 14 . 
     
     
         16 . A pharmaceutical combination comprising the compound of  claim 1  and a second anti-platelet or cardiovascular agent. 
     
     
         17 . The combination according to  claim 16 , wherein the second antiplatelet or cardiovascular agent is selected from the group consisting of aspirin, cilostazol and dipyridamole. 
     
     
         18 . A pharmaceutical formulation comprising the compound of  claim 1  and a gastric pH regulating agent. 
     
     
         19 . The pharmaceutical formulation according to  claim 18 , wherein the gastric pH regulating agent is selected from the group consisting of a proton pump inhibitor and ranitidine. 
     
     
         20 . A method of treatment or prophylaxis of thrombosis or embolisms in a subject in need of such treatment comprising administering the compound of  claim 1 .