Prodrugs of anti-platelet agents

Abstract

The invention relates to the compounds of formula II, formula Ia, formula IIa or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula II, formula Ia, formula IIa and methods for treating or preventing atherothrombosis may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment or management of ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovascular diseases and blood clots.

1 . A compound of Formula II: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, hydrate, polymorph, solvate, prodrug, enantiomer, or stereoisomer thereof, wherein: 
       R 1  represents 
       
         
           
           
               
               
           
         
       
       R 2  represents 
       
         
           
           
               
               
           
         
       
       a is 2, 3 or 7; 
       each b is independently 3, 5 or 6; 
       e is 1, 2 or 6; and 
       c and d are each independently H, D, —OH, —OD, C 1 -C 6 -alkyl, —NH 2  or —COCH 3 . 
     
     
         2 . A compound of Formula Ia: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, hydrate, polymorph, solvate, prodrug, enantiomer, or stereoisomer thereof, wherein: 
       R 1  represents 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       R 2  represents 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         a is 2, 3 or 7; 
         each b is independently 3, 5 or 6; 
         e is 1, 2 or 6; and 
         c and d are each independently H, D, —OH, —OD, C 1 -C 6 -alkyl, —NH 2  or —COCH 3 . 
       
     
     
         3 . A compound of Formula IIa: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, hydrate, polymorph, solvate, prodrug, enantiomer, or stereoisomer thereof, wherein: 
       R 1  independently represents 
       
         
           
           
               
               
           
         
       
       R 2  represents 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       a is 2, 3 or 7; 
       each b is independently 3, 5 or 6; 
       e is 1, 2 or 6; and 
       c and d are each independently H, D, —OH, —OD, C 1 -C 6 -alkyl, —NH 2  or —COCH 3 . 
     
     
         4 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein said pharmaceutical composition is formulated to treat an underlying etiology with an effective amount administering the patient in need by oral administration, delayed release or sustained release, transmucosal administration, syrup, topical administration, parenteral administration, injection, subdermal administration, oral solution, rectal administration, buccal administration or transdermal administration. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the underlying etiology is atherothrombosis, ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovascular diseases and blood clots. 
     
     
         7 . A pharmaceutical composition comprising a compound of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration, delayed release or sustained release, transmucosal, syrup, topical, parenteral administration, injection, subdermal, oral solution, rectal administration, buccal administration or transdermal administration. 
     
     
         9 . Compounds and compositions of  claim 8 , wherein said compounds and compositions are formulated for the treatment or management of the underlying etiology such as atherothrombosis, ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovascular diseases and blood clots. 
     
     
         10 . A pharmaceutical composition comprising a compound of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein said pharmaceutical composition is formulated to treat an underlying etiology with an effective amount administering the patient in need by oral administration, delayed release or sustained release, transmucosal administration, syrup, topical administration, parenteral administration, injection, subdermal administration, oral solution, rectal administration, buccal administration or transdermal administration. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the underlying etiology is such as atherothrombosis, ischemia, stroke, cerebral thrombosis, arterial thrombosis, thrombotic cerebrovascular, cardiovascular diseases and blood clots.