Hepatitis C inhibitor peptide analogues

A compound of formula I:

• ##STR64## wherein B is an acyl derivative of formula R.sub.11 --C(O)-- wherein R.sub.11 is C.sub.1-10 alkyl optionally substituted with carboxyl;
• or R.sub.11 is C.sub.6 or C.sub.10 aryl or C.sub.7-16 aralkyl optionally substituted with a
• C.sub.1-6 alkyl;
• a is 0 or 1;
• R.sub.6, when present, is the side chain of Asp or Glu,
• b is 0 or 1;
• R.sub.5, when present, is the side chain of D-Asp, D-Val, or D-Glu;
• Y is H or C.sub.1-6 alkyl;
• R.sub.4 is C.sub.1-10 alkyl or C.sub.3-10 cycloalkyl;
• R.sub.3 is C.sub.1-10 alkyl or C.sub.3-10 cycloalkyl;
• W is a group of formula II':
• ##STR65## wherein X' is N;
• and R.sub.2 ' is the side chain of proline and is substituted with R.sub.17 at the 4-position with thc stereochemistry shown in formula III':
• ##STR66## wherein R.sub.17 is C.sub.6 or C.sub.10 aryl, C.sub.7-16 aralkyl, S--C.sub.6 or C.sub.10 aryl or S--C.sub.7-16 aralkyl, each optionally substituted with C.sub.1-6 alkyl, NH.sub.2, OH, SH, halo, carboxyl or carboxy(lower)alkyl, said aryl or aralkyl optionally containing at least one heteroatom selected independently from the group consisting of:
• O, S, and N;
• and said aryl and aralkyl optionally fused with a second 5-, 6- or 7-membered ring to form cyclic system or heterocycle, said second ring being optionally substituted with NH.sub.2, OH, SH, halo, carboxy or carboxy(lower)alkyl, and said second ring optionally containing at least one heteroatom selected independently from the group consisting of:
• O, S, and N;
• or R.sub.17 is OR.sub.12 wherein R.sub.12 is a C.sub.6 or C.sub.10 aryl or C.sub.7-16 aralkyl said first aryl or aralkyl optionally substituted with C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, NH.sub.2, OH, SH, halo, C.sub.1-6 alkoxy, carboxyl, carboxy(lower)alkyl, or a second aryl or aralkyl;
• said first and second aryl or aralkyl optionally containing at least one heteroatom selected independently from the group consisting of:
• O, S, and N;
• Q is a group of the formula:
• ##STR67## wherein Z is CH or N;
• X is O or S;
• R.sub.1 is H, C.sub.1-6 alkyl or C.sub.1-6 alkenyl both optionally substituted with thio or halo;
• and
• when Z is CH, then R.sub.13 is H;
• CF.sub.3 ;
• CF.sub.2 CF.sub.3 ;
• CH.sub.2 --R.sub.14 ;
• CH(F)--R.sub.14 ;
• CF.sub.2 --R.sub.14 ;
• NR.sub.14 R.sub.14 ';
• S--R.sub.14 ;
• or CO--NH--R.sub.14, wherein
• R.sub.14 and R.sub.14 ' are independently hydrogen, cyclic C.sub.3-10 alkyl or acyclic C.sub.1-10 alkyl or cyclic C.sub.3-10 alkenyl or acyclic C.sub.2-10 alkenyl, said alkyl or alkenyl optionally substituted with NH.sub.2, OH, SH, halo or carboxyl;
• said alkyl or alkenyl optionally containing at least one heteroatom selected independently from the group consisting of:
• O, S, and N;
• or
• R.sub.14 and R.sub.14 ' are independently C.sub.6 or C.sub.10 aryl or C.sub.7-16 aralkyl optionally substituted with C.sub.1-6 alkyl, NH.sub.2, OH, SH, halo, carboxyl or carboxy(lower)alkyl or substituted with a further C.sub.3-7 cycloalkyl, C.sub.6 or C.sub.10 aryl, or heterocycle;
• said aryl or aralkyl optionally containing at least one heteroatom selected independently from the group consisting of:
• O, S, and N.;
• said cyclic alkyl, cyclic alkenyl, aryl or aralkyl being optionally fused with a second 5-, 6-, or 7-membered ring to form a cyclic system or heterocycle, said second ring being optionally substituted with NH.sub.2, OH, SH, halo, carboxyl or carboxy(lower)alkyl or substituted with a further C.sub.3-7 cycloalkyl, C.sub.6 or C.sub.10 aryl, or heterocycle;
• said second ring optionally containing at least one heteroatom selected independently from the group consisting of:
• O, S, and N;
• or R.sub.14 and R.sub.14 ' are independently C.sub.1-4 alkyl which when joined together with N form a 3 to 6-membered nitrogen-containing ring which is optionally fused with a further C.sub.3-7 cycloalkyl, C.sub.6 or C.sub.10 aryl or heterocycle;
• with the proviso that when Z is CH, R.sub.13 is N(R.sub.14)R.sub.14 ', R.sub.14 is H and R.sub.14 ' is cyclic C.sub.3-10 alkyl or acyclic C.sub.1-10 alkyl or cyclic C.sub.3-10 alkenyl or acyclic C.sub.2-10 alkenyl, each substituted with carboxyl, then said carboxyl is not on the .alpha.-carbon of said alkyl or alkenyl and R.sub.13 is not an .alpha.-amino acid;
• when Z is N, then R.sub.13 is H;
• carboxy;
• C.sub.1-6 alkyl optionally substituted with carboxy;
• CH.sub.2 --R.sub.14 ;
• CHR.sub.14 R.sub.14 ';
• CH(F)--R.sub.14 ;
• O--R.sub.14 ;
• NR.sub.14 R.sub.14 ' or S--R.sub.14, wherein R.sub.14 and R.sub.14 ' are as defined above;
• or
• Q is a phosphonate group of the formula:
• ##STR68## wherein R.sub.15 and R.sub.16 are independently C.sub.6-20 aryloxy;
• and R.sub.1A is the same as R.sub.1 as defined above.