EP1437362A1 — Macrocyclic peptides inhibiting the hepatitis C virus ns3 protease

USPTO 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 is CH or N; R 21 is H, halo, C 1-6 alkyl, cycloalkyl, haloalkyl, C 1-6 alkoxy, cycloalkoxy, hydroxy, or N( R 23 ) 2 , wherein each R 23 is independently H, C 1-6 alkyl or cycloalkoxy; and 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, 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)-O R 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)-O R 32 or -C(O)-NH R 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, cycloalkyl or -C(O)- R 42 , wherein R 42 is C 1-6 alkyl, 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 or 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 or C 7-16 aralkyl; or A is a carboxylic acid or a pharmaceutically acceptable salt or ester thereof.