Depeptidized inhibitors of hepatitis C virus NS3 protease

A compound having the general structure shown in Formula 2:

• or a pharmaceutically acceptable salt, or ester thereof, wherein,
• M is O, N(H), or CH2;
• R1 is —OR6, —NR6R7 or
• where R6 and R7 can be the same or different, each being independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, hydroxyl, amino, arylamino and alkylamino;
• P1 is selected from the group consisting of alkyl, alkenyl, alkynyl, (C3-C10)cycloalkyl haloalkyl;
• P3 is selected from the group consisting of alkyl, (C3-C10)cycloalkyl, aryl and (C3-C10)cycloalkyl fused with aryl;
• R4 and R5 can be the same or different, each being independently selected from the group consisting of H, alkyl, aryl and (C3-C10)cycloalkyl;
• or alternatively R4 and R5 together form part of a cyclic 5- to 7-membered ring such that the moiety
• is represented by
• where k is 0 to 2;
• X is selected from the group consisting of:
• where p is 1 to 2, q is 1 to 3 and P2 is alkyl, aryl, heteroaryl, heteroalkyl, (C3-C10)cycloalkyl, dialkylamino, alkylamino, arylamino or (C3-C10)cycloalkylamino;
• and
• R3 is selected from the group consisting of:
• aryl, heterocyclyl, heteroaryl,
• where Y is O, S or NH, and Z is CH or N, and the R8 moieties can be the same or different, each R8 being independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, (C3-C10)cycloalkyl, aryl, heteroaryl, heterocyclyl, hydroxyl, amino, arylamino, alkylamino, dialkylamino, halo, alkylthio, arylthio and alkyloxy;
• wherein each of said heteroaryl and said heterocyclyl consist of 4-14 ring atoms, wherein 1 to 4 of said ring atoms are O, N, or S, further wherein each of said heteroaryl and heterocylyl can be monocyclic or bicyclic and;
• heteroalkyl is (C1-C12) alkyl, wherein 1-4 of the (C1-12) atoms are replaced by heteroatoms selected from the group consisting of O, N and S.

A compound having the general structure shown in Formula 3:

• or a pharmaceutically acceptable salt, or ester thereof, wherein,
• M is O, N(H), or CH2;
• n is 0-4;
• R1 is —OR6, —NR6R7 or
• where R6 and R7 can be the same or different, each being independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, hydroxyl, amino, arylamino and alkylamino;
• R4 and R5 can be the same or different, each being independently selected from the group consisting of H, alkyl, aryl and (C3-C10)cycloalkyl;
• or alternatively R4 and R5 together form part of a cyclic 5- to 7-membered ring such that the moiety
• is represented by
• where k is 0 to 2;
• X is selected from the group consisting of:
• where p is 1 to 2, q is 1 to 3 and P2 is alkyl, aryl, heteroaryl, heteroalkyl, (C3-C10)cycloalkyl, dialkylamino, alkylamino, arylamino or (C3-C10)cycloalkylamino;
• and
• R3 is selected from the group consisting of:
• aryl, heterocyclyl, heteroaryl,
• where Y is O, S or NH, and Z is CH or N, and the R8 moieties can be the same or different, each R8 being independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, (C3-C10)cycloalkyl, aryl, heteroaryl, heterocyclyl, hydroxyl, amino, arylamino, alkylamino, dialkylamino, halo, alkylthio, arylthio and alkyloxy;
• wherein each of said heteroaryl and said heterocyclyl consist of 4-14 ring atoms, wherein 1 to 4 of said ring atoms are O, N, or S, further wherein each of said heteroaryl and heterocylyl can be monocyclic or bicyclic and;
• heteroalkyl is (C1-C12) alkyl, wherein 1-4 of the (C1-12) atoms are replaced by heteroatoms selected from the group consisting of O, N and S.