Macrocyclic peptides active against the hepatitis C virus

Abstract

The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R 21 , R 22 , R 3 , R 4 , D and A are as defined herein, or a pharmaceutically acceptable salt or ester thereof.

What is claimed is:  
     
         1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
         wherein W is CH or N,  
         R 21  is H, halo, C 1-6  alkyl, C 3-6  cycloalkyl, C 1-6  haloalkyl, C 1-6  alkoxy, C 3-6  cycloalkoxy, hydroxy, or N(R 23 ) 2 , wherein each R 23  is independently H, C 1-6  alkyl or C 3-6  cycloalkyl;  
         R 22  is H, halo, C 1-6  alkyl, C 3-6  cycloalkyl, C 1-6  haloalkyl, C 1-6  thioalkyl, C 1-6  alkoxy, C 3-6  cycloalkoxy, C 2-7  alkoxyalkyl, C 3-6  cycloalkyl, C 6 or 10  aryl or Het, wherein Het is a five-, six-, or seven-membered saturated or unsaturated heterocycle containing from one to four heteroatoms selected from nitrogen, oxygen and sulfur;  
         said cycloalkyl, aryl or Het being substituted with R 24 ,  
         wherein R 24  is H, halo, C 1-6  alkyl, C 3-6  cycloalkyl, C 1-6  alkoxy, C 3-6  cycloalkoxy, NO 2 , N(R 25 ) 2 , NH—C(O)—R 25  or NH—C(O)—NH—R 25 , wherein each R 25  is independently: H, C 1-6  alkyl or C 3-6  cycloalkyl;  
         or R 24  is NH—C(O)—OR 26  wherein R 26  is C 1-6  alkyl or C 3-6  cycloalkyl;  
         R 3  is hydroxy, NH 2 , or a group of formula —NH—R 31 , wherein R 31  is C 6 or 10  aryl, heteroaryl, —C(O)—R 32 , —C(O)—NHR 32  or —C(O)—OR 32 ,  
         wherein R 32  is C 1-6  alkyl or C 3-6  cycloalkyl;  
         D is a 5 to 10-atom saturated or unsaturated alkylene chain optionally containing one to three heteroatoms independently selected from: O, S, or N—R 41 , wherein 
 R 41  is H, C 1-6  alkyl, C 3-6  cycloalkyl or —C(O)—R 42 , wherein R 42  is C 1-6  alkyl, C 3-6  cycloalkyl or C 6 or 10  aryl;  
 R 4  is H or from one to three substituents at any carbon atom of said chain D, said substituent independently selected from the group consisting of: C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  alkoxy, hydroxy, halo, amino, oxo, thio and C 1-6  thioalkyl, and  
 A is an amide of formula —C(O)—NH—R 5 , wherein R 5  is selected from the group consisting of: C 1-8  alkyl, C 3-6  cycloalkyl, C 6 or 10  aryl and C 7-16  aralkyl;  
 or A is a carboxylic acid or a pharmaceutically acceptable salt or ester thereof.