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 pharmaceutical composition comprising a substantially pure compound of Formula IIA, or salts thereof, wherein the asterisks denote chiral carbon centers having a (S,S) absolute stereochemical configuration: 
       
         
           
           
               
               
           
         
       
       and one or more pharmaceutical excipients. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the compound of Formula II is substantially free from its isomers of Formulas IIB, VI and VII, wherein the asterisks in Formula IIB denote chiral carbon centers: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the isomers of Formula IIB, VI or VII either individually or cumulatively are less than 10% by weight of the total compound. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the isomers of Formula IIB, VI or VII either individually or cumulatively are less than 3% by weight of the total compound. 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the other isomers of Formula IIB, VI or VII either individually or cumulatively are less than 2.0% by weight of the total compound. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the salt is selected from the group consisting of hydrogen sulfate, methane sulfonate and benzene sulfonate. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein said composition is an oral dosage form. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein said composition is a tablet or capsule. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the composition contains one or more of drugs selected from the group consisting of aspirin, statins, cilostazol and dipyridamole. 
     
     
         10 . The pharmaceutical composition of  claim 1 , further comprising a gastric pH regulating agent. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the gastric pH regulating agent is selected from the group consisting of a proton pump inhibitor, and ranitidine. 
     
     
         12 . A method of treatment or prophylaxis of thrombosis or embolisms in a subject in need of such treatment comprising administering the composition of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the treatment alleviates or minimizes inter individual platelet response variability and metabolic loading in the subject. 
     
     
         14 . The method of  claim 13 , wherein inter individual platelet response variability is due to CYP450 polymorphism. 
     
     
         15 . The method of  claim 13 , wherein the CYP450 polymorphism is CYP2C19*2 or CYP2C19*17. 
     
     
         16 . A method according to  claim 12 , wherein the inter individual platelet response variability is due to P glycoprotein efflux transports.