P1-nonepimerizable ketoamide inhibitors of hcv ns3 protease

A compound, or enantiomer, stereoisomer, rotamer, tautomer, or racemate of said compound, or a pharmaceutically acceptable salt, solvate or ester of said compound, said compound having the general structure shown in Formula I:

• wherein:
• R1 and R2 are independently H, alkyl-, alkenyl-, alkynyl-, cycloalkyl-, cycloalkenyl-, heteroalkyl-, heterocyclyl-, heterocycloalkenyl, aryl-, heteroaryl-, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, arylalkyl-, arylalkenyl-, heteroarylalkyl-, heteroarylalkenyl-, alkoxy, aryloxy, alkylthio, arylthio, amino, hydroxyl, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, halogen, alkylaryl, alkylheteroaryl, alkenylaryl, and alkenylheteroaryl, wherein each of said alkyl-, alkenyl-, alkynyl, cycloalkyl-, cycloalkenyl-, heteroalkyl-, heterocyclyl-, heterocycloalkenyl, aryl-, heteroaryl-, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, arylalkyl-, arylalkenyl-, heteroarylalkyl-, and heteroarylalkenyl- can be unsubstituted or substituted with one or more moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, monohaloalkyl, dihaloalkyl, trihaloalkyl, halogen aryl, arylalkyl, cycloalkyl, heterocycloalkyl, hydroxyl, thio, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfamido, sulfoxide, sulfone, sulfonylurea, hydrazide, and hydroxamate;
• A and M can be the same or different, each being independently selected from hydrogen, alkoxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclyl, heterocycloalkenyl, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, —COOR9, —CONR9, wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclyl, heterocycloalkenyl, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, and heterocycloalkenylalkenyl- can be unsubstituted or substituted with one or moieties, which can be the same or different, each moiety being independently selected from the group consisting of halogen, nitro, alkyl, amino, aryl, trihaloalkyl, dihaloalkyl, and monohaloalkyl;
• or
• A and M are connected to each other such that the moiety:
• shown above in Formula I forms either a three, four, five, six, seven or eight-membered cycloalkyl, a four to eight-membered heterocyclyl, a six to ten-membered aryl, or a five to ten-membered heteroaryl, wherein each of said three, four, five, six, seven or eight-membered cycloalkyl, a four to eight-membered heterocyclyl, a six to ten-membered aryl, or a five to ten-membered heteroaryl can be unsubstituted or substituted with R10,
• R10 is one or more moieties, which can be the same or different, each moiety being independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, —COOR9, and —CONR9;
• R3 can be one or more moieties, which can be the same or different, independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, cycloalkyl-, cycloalkenyl-, heteroalkyl-, heterocyclyl-, heterocycloalkenyl, aryl-, heteroaryl-, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, arylalkyl-, arylalkenyl-, heteroarylalkyl-, heteroarylalkenyl-, alkoxy, aryloxy, alkylthio, arylthio, amino, hydroxyl, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, halogen, alkylaryl, alkylheteroaryl, alkenylaryl, and alkenylheteroaryl, wherein each of said alkyl-, alkenyl-, alkynyl, cycloalkyl-, cycloalkenyl-, heteroalkyl-, heterocyclyl-, heterocycloalkenyl, aryl-, heteroaryl-, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, arylalkyl-, arylalkenyl-, heteroarylalkyl-, and heteroarylalkenyl- can be unsubstituted or substituted with one or more moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, monohaloalkyl, dihaloalkyl, trihaloalkyl, halogen aryl, arylalkyl, cycloalkyl, heterocycloalkyl, hydroxyl, thio, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfamido, sulfoxide, sulfone, sulfonylurea, hydrazide, and hydroxamate;
• R6 is one or two moieties, which can be the same or different, independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, cycloalkyl-, cycloalkenyl-, heteroalkyl-, heterocyclyl-, heterocycloalkenyl, aryl-, heteroaryl-, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, arylalkyl-, arylalkenyl-, heteroarylalkyl-, heteroarylalkenyl-, alkoxy, aryloxy, alkylthio, arylthio, amino, hydroxyl, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, halogen, alkylaryl, alkylheteroaryl, alkenylaryl, and alkenylheteroaryl, wherein each of said alkyl-, alkenyl-, alkynyl, cycloalkyl-, cycloalkenyl-, heteroalkyl-, heterocyclyl-, heterocycloalkenyl, aryl-, heteroaryl-, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, heterocyclylalkyl-, heterocyclylalkenyl-, heterocycloalkenylalkyl-, heterocycloalkenylalkenyl-, arylalkyl-, arylalkenyl-, heteroarylalkyl-, and heteroarylalkenyl- can be unsubstituted or substituted with one or more moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, monohaloalkyl, dihaloalkyl, trihaloalkyl, halogen aryl, arylalkyl, cycloalkyl, heterocycloalkyl, hydroxyl, thio, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfamido, sulfoxide, sulfone, sulfonylurea, hydrazide, and hydroxamate;
• W is
• Y is
• wherein R7 and R8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl-, thiophenyl, and thiazolyl, wherein each of said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl-, cycloalkenylalkyl-, cycloalkylalkenyl-, cycloalkenylalkenyl, thiophenyl, and thiazolyl can be can be unsubstituted or substituted with one or moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, amino, hydroxyl, trihaloalkyl, dihaloalkyl, and monohaloalkyl;
• or
• R7 and R8 together with the carbon to which they are attached form either a three, four, five, six, seven and eight-membered cycloalkyl, a four to eight-membered heterocyclyl, three to eight-membered cycloalkenyl, a four to eight-membered heterocycloalkenyl, a six to ten membered aryl, or a five to ten-membered heteroaryl, wherein each of said three to eight-membered cycloalkyl, four to eight-membered heterocyclyl, three to eight-membered cycloalkenyl, four to eight-membered heterocycloalkenyl, six to ten membered aryl, or five to ten-membered heteroaryl can be unsubstituted or substituted with one or more moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, monohaloalkyl, dihaloalkyl, trihaloalkyl and halogen;
• or
• Y is —O—R9;
• X is selected from the group consisting of:
• alkyl, alkenyl, and alkynyl, wherein each of said alkyl, alkenyl, and alkynyl can be unsubstituted or substituted with one or more moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, monohaloalkyl, dihaloalkyl, trihaloalkyl and halogen,
• V and R9 are independently selected from the group consisting of hydrogen alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycloalkenyl, heterocyclyl, heteroalkyl, cycloalkyl, cycloalkenyl and wherein each of said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycloalkenyl, heterocyclyl, heteroalkyl, cycloalkyl and cycloalkenyl can be unsubstituted or substituted with one or moieties, which can be the same or different, each moiety being independently selected from the group consisting of alkyl, alkenyl, alkynyl, amino, hydroxyl, trihaloalkyl, dihaloalkyl, and monohaloalkyl;
• or
• n is 0 to 5;
• m is 0 to 4.