Novel macrocyclic inhibitors of hepatitis c virus replication

A compound having the structure of Formula I:

• or a pharmaceutically acceptable salt or prodrug thereof wherein:
• R1 is selected from the group consisting of substituted aryl, substituted heteroaryl, —C(O)OR4, —C(O)NR5R6, —C(O)R7, and
• R2 is selected from the group consisting of alkyl, —C(O)-alkyl,
• R3 is selected from the group consisting of —OR9 and —SO2R10;
• R4 is selected from the group consisting of alkyl, heterocyclyl, and aryl;
• R5 is alkyl and R6 is selected from the group consisting of alkyl and aralkyl, or R5 together with R6 form an optionally substituted heterocyclyl or optionally substituted heteroaryl;
• R7 is phenyl substituted one or more times with halogen;
• R8 is selected from the group consisting of —CF3 and methyl;
• R9 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aryl, and optionally substituted aralkyl;
• R10 is selected from the group consisting of alkyl optionally substituted with alkoxy or alkenyl, optionally substituted aryl, optionally substituted aralkyl, substituted heteroaryl, and
• R11 and R12 are each hydrogen or together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl;
• X is halogen and is present 1 to 4 times;
• and
• Z1 and Z2 are independently selected from the group consisting of —CH2—, —CF2—, and —O— provided that at least one of Z1 and Z2 is —CH2—;
• provided that if R11 and R12 are each hydrogen, R2 is alkyl, and R3 is —SO2-cyclopropyl, then R1 is not —C(O)O-t-butyl;
• provided that if R11 and R12 are each hydrogen and R2 is
• then R3 is —SO2-phenyl disubstituted with halogen or —SO2-thiophene disubstituted with halogen, or R1 is
• where R8 is —CF3;
• provided that if R11 and R12 are each hydrogen, R2 is
• and R3 is —SO2-cyclopropyl, then R1 is not —C(O)O-t-butyl, —C(O)O-haloalkyl, or —C(O)O-cyclopentyl;
• provided that if R11 and R12 are each hydrogen, R2 is
• and R3 is substituted —SO2-heteroaryl, then R1 is not —C(O)O-cyclopentyl;
• provided that if R11 and R12 are each hydrogen, R2 is
• and R3 is —SO2-cyclopropyl, then R1 is not —C(O)O-alkyl or —C(O)O-heterocyclyl;
• provided that if R11 and R12 are each hydrogen, R2 is
• and R3 is —SO2-alkyl or optionally substituted —SO2-aryl, then R1 is not —C(O)O-cycloalkyl;
• provided that if R11 and R12 are each hydrogen, R2 is
• and R3 is optionally substituted —SO2-phenyl, then R1 is not —C(O)O-t-butyl;
• provided that if R11 and R12 are each hydrogen, R2 is
• and R3 is —SO2-alkyl substituted with alkoxy or alkenyl, then R1 is —C(O)O-t-butyl and X is F;
• and
• provided that the compound of formula (I) is not selected from the group consisting of: