MAKROZYKLISCHE PEPTIDE ALS HEPATITIS C VIRUS NS3 PROTEASE INHIBITORE

摘要

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, C1-6 alkyl, cycloalkyl, haloalkyl, C1-6 alkoxy, cycloalkoxy, hydroxy, or N(R<23>)2, wherein each R<23> is independently H, C1-6 alkyl or cycloalkoxy; and R<22> is H, halo, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 thioalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, C2-7 alkoxyalkyl, C3-6 cycloalkyl, C6 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, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, NO2, N(R<25>)2, NH-C(O)-R<25>; or NH-C(O)-NH-R<25>, wherein each R<25> is independently: H, C1-6 alkyl or C3-6 cycloalkyl; or R<24> is NH-C(O)-OR<26> wherein R<26> is C1-6 alkyl or C3-6 cycloalkyl; R<3> is hydroxy, NH2, or a group of formula -NH-R<31>, wherein R<31> is C6 or 10 aryl, heteroaryl, -C(O)-R<32>, -C(O)-OR<32> or -C(O)-NHR<32>, wherein R<32> is: C1-6 alkyl or C3-6 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, C1-6 alkyl, cycloalkyl or -C(O)-R<42>, wherein R<42> is C1-6 alkyl, cycloalkyl or C6 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: C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, hydroxy, halo, amino, oxo, thio or C1-6 thioalkyl, and A is an amide of formula -C(O)-NH-R<5>, wherein R<5> is selected from the group consisting of: C1-8 alkyl, C3-6 cycloalkyl, C6 or 10 aryl or C7-16 aralkyl; or A is a carboxylic acid or a pharmaceutically acceptable salt or ester thereof.