Peptides as NS3-serine protease inhibitors of hepatitis C virus

A compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound having the general structure shown in Formula I:

• wherein:
• Y is selected from the group consisting of the following moieties:
• alkyl, alkyl-aryl, heteroalkyl, heteroaryl, arylheteroaryl, alkyl-heteroaryl, cycloalkyl, alkyloxy, alkylaryloxy, aryloxy, heteroaryloxy, heterocycloalkyloxy, cycloalkyloxy, alkylamino, arylamino, alkyl-arylamino, arylamino, heteroarylamino, cycloalkylamino and heterocycloalkylamino, with the proviso that Y may be optionally substituted with X11 or X12;
• X11 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, alkylaryl, arylalkyl, heteroaryl, alkylheteroaryl, or heteroarylalkyl, with the proviso that X11 may be additionally optionally substituted with X12;
• X12 is hydroxy, alkoxy, aryloxy, thio, alkylthio, arylthio, amino, alkylamino, arylamino, alkylsulfonyl, arylsulfonyl, alkylsulfonamido, arylsulfonamido, carboxy, carbalkoxy, carboxamido, alkoxycarbonylamino, alkoxycarbonyloxy, alkylureido, arylureido, halogen, cyano, or nitro, with the proviso that said alkyl, alkoxy, and aryl may be additionally optionally substituted with moieties independently selected from X12;
• R1 is COR5 wherein R5 is COOR8, CONR9R10, CF3, C2F5, C3F7, CF2R6, or R6, wherein R6, R8, R9 and R10 are independently selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl, [CH(R1′)]pCOOR11, [CH(R1′)] pCONR12R13, [CH(R1′)]pSO2R11, [CH(R1′)]pCOR11, [CH(R1′)]pCH(OH)R11, CH(R1′)CONHCH(R2′) COO R11, CH(R1′)CONHCH(R2′)CONR12R13, CH(R1′)CONHCH(R2′)R′, CH(R1′)CONHCH(R2′)CONHCH(R3′) COO R11, CH(R1′)CONHCH(R2′)CONHCH(R3′) CONR12R13, CH(R1′)CONHCH(R2′)CONHCH(R3′) CONHCH(R4′) COO R11, CH(R1′)CONHCH(R2′)CONHCH(R3′)CONHCH(R4′)CONR12R13, CH(R1′)CONHCH(R2′)CONHCH(R3′) CONHCH(R4′) CONHCH(R5′)COO R11 and CH(R1′)CONHCH(R2′)CONHCH(R3′)CONHCH(R4′)CONHCH(R5′)CONR12R13, wherein R1′, R2′, R3′, R4′, R5′, R11, R12, and R13 are independently selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, alkyl-aryl, alkylheteroaryl, aryl-alkyl and heteroaralkyl;
• Z is selected from O, N, CH or CR;
• W may be present or absent, and if W is present, W is selected from C═O, C═S, C(═N—CN), or SO2;
• Q may be present or absent, and when Q is present, Q is CH, N, P, (CH2)p, (CHR)p, (CRR′)p, O, NR, S, or SO2;
• and when Q is absent, M may be present or absent;
• when Q and M are absent, A is directly linked to L;
• A is O, CH2, (CHR)p, (CHR—CHR′)p, (CRR′)p, NR, S, or SO2;
• E is CH, N, CR, or a double bond towards or L;
• G is absent, and E is directly connected to the carbon atom in Formula I as G is linked to;
• J is present, J is (CH2)p, (CHR) p, or (CRR′)p, SO2, NH, NR or O;
• L is present, L is CH, CR, O, S or NR;
• M may be present or absent, and when M is present, M is O, NR, S, SO2, (CH2)p, (CHR)p (CHR—CHR′)p, or (CRR′)p;
• p is a number from 0 to 6;
• and
• R, R′, R2, R3 and R4 are independently selected from the group consisting of H;
• C1–C10 alkyl;
• C2–C10 alkenyl;
• C3–C8 cycloalkyl;
• C3–C8 heterocycloalkyl, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, halogen;
• (cycloalkyl)alkyl and (heterocycloalkyl)alkyl, wherein said cycloalkyl is made of three to eight carbon atoms, and zero to six oxygen, nitrogen, sulfur, or phosphorus atoms, and said alkyl is of one to six carbon atoms;
• aryl;
• heteroaryl;
• alkyl-aryl;
• alkylheteroaryl;
• and further with respect to R2, the group
• wherein said alkyl, heteroalkyl, alkenyl, heteroalkenyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties may be optionally and chemically-suitably substituted, with said term “substituted” referring to optional and chemically-suitable substitution with one or more moieties selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, heterocyclic, halogen, hydroxy, thio, alkoxy, aryloxy, alkylthio, arylthio, amino other than for R2, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfonamido, sulfoxide, sulfone, sulfonyl urea, hydrazide, and hydroxamate;
• further wherein said unit N-C-E-L-J-N represents a five-membered or six-membered cyclic ring structure with the proviso that when said unit N-C-E-L-J-N represents a five-membered cyclic ring structure, or when the bicyclic ring structure in Formula I comprising N, C, E, L, J, N, A, Q, and M represents a five-membered cyclic ring structure, then said five-membered cyclic ring structure lacks a carbonyl group as part of the cyclic ring.