Inhibitors of cysteine proteases and methods of use thereof

Abstract

The disclosure provides compounds, such as compounds of Formula II, with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.

1 . A compound represented by: 
       
         
           
           
               
               
           
         
         wherein: 
         R 3a  is 
       
       
         
           
           
               
               
           
         
         R 3b  is hydrogen; 
         A is cyano; 
         X is CH; 
         R 3  is: 
       
       
         
           
           
               
               
           
         
         R 2  is —NHC(O)R B ; and where R 1a  and R 2  are joined together to form, with the carbon to which they are attached, a 4-10 membered heterocycle represented by: 
       
       
         
           
           
               
               
           
         
         R B  is C 1 -C 8 alkyl substituted by —N(R y )C(O)R y ; 
         R y  is independently selected, for each occurrence, from H and C 1 alkyl; 
         R 2  is substituted on R B  by one, two or three R x  substituents, where the R x  substituent is independently selected for each occurrence from the group consisting of halogen and hydroxyl; 
         R 1b  is hydrogen. 
       
     
     
         2 . The compound of  claim 1 , wherein the R x  substituent is halogen, and R 2  is substituted on R B  by three halogens.