Multisubstituted aromatic compounds as inhibitors of thrombin

Abstract

There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing a disease or disorder, which disease or disorder is amenable to treatment or prevention by the inhibition of thrombin.

What is claimed is: 
     
         1 . A compound with structure of Formula (Ia): 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt, ester, solvate, or prodrug thereof; 
         wherein 
         ring A is substituted or unsubstituted pyrazolyl, or substituted or unsubstituted triazolyl; 
         L 1 , L 2  and L 3  are independently a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, —S—, —SO—, —SO 2 —, —O—, —NHSO 2 —, or —NR—; 
         L 4  is absent, a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, —S—, —SO—, —SO 2 —, —O—, —NHSO 2 —, or —NR 5 —; 
         R 1 , R 2  and R 3  are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         R 4  is absent, hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, provided that when L 4  is absent, then R 4  is absent; and 
         R 5  is independently hydrogen, or substituted or unsubstituted alkyl.