Antifibrinolytic compounds

Abstract

The present invention provides novel antifibrinilytic compounds, processes for their preparation, pharmaceutical and veterinary compositions thereof, and their use in medicine, in particular for the treatment of bleeding.

1 . A compound of formula III:
   R 1 —CH 2 —X 1 —R 5   (III)
   wherein:
 R 1  is —NH 2 , —NHR 6 , NR 6 R 7  —N + R 6 R 7 R 8  or —S + R 9 R 10 ; 
 R 5  is —C(O)R 12 , —SO 2 R 13 , —P(O)R 14 R 15 , nitro or nitroso; 
 R 6 , R 7 , R8, R 9  and R 10  are independently (C 1 -C 4 )alkyl or halo(C 1 -C 4 )alkyl, or R 6  and R 7 , together with the N atom to which they are attached form an aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, or pyrrolyl group; 
 R 12 , R 13 , R 14  and R 15  are independently hydroxyl, —O—(C 1 -C 4 )alkyl or —(C 1 -C 4 )alkyl; and 
 X 1  is trans cyclohexan-1,4-diyl; 
 with the proviso that R 1  in not NH 2  when R 2  is COOH, or 
 a pharmaceutically acceptable salt thereof. 
   
     
     
         2 . The compound of  claim 1 , of formula IIIa:
   R 9 R 10 S + —CH 2 —X—R 5   (IIIa)
   or a pharmaceutically acceptable salt thereof.   
     
     
         3 . The compound of  claim 1 , of formula IIIb:
   R 9 R 10 S + —CH 2 —X 1 —C(O)R 12   (IIIb)
   or a pharmaceutically acceptable salt thereof.   
     
     
         4 . The compound of  claim 1 , wherein R 12  is hydroxyl or —O—(C 1 -C 4 )alkyl or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The compound of  claim 4 , wherein R 12  is hydroxyl, or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The compound according to  claim 1 , wherein. R 9  and R 10  are independently (C 1 -C 2 )alkyl or halo(C 1 -C 2 )alkyl, or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The compound of  claim 6 , wherein R 9  and R 10  are both methyl, or a pharmaceutically acceptable salt thereof.