Fluorinated tripeptide HCV serine protease inhibitors
AssigneeEnanta Pharmaceuticals, Inc.
InventorsYonghua Gai, Yat Sun Or, Zhe Wang
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Abstract
The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis c virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis c virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
Claims19
A compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- M is absent, O, S, S(O), SO2, NH, O(CO), NH(CO), NH(CO)NH, NHSO2, NHSO2NH, NH(CO)O, alkylene, substituted alkylene, alkenylene or substituted alkenylene;
- Cy is selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl;
- substituted heteroaryl, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl wherein
- G is -E-R3, where E is absent or E is O, CO, (CO)O, (CO)NH, NR5, NH(CO), NH(CO)NH, NH(SO2)NH or NHSO2;
- R3 is selected from the group consisting of:
- a) hydrogen;
- b) aryl;
- c) substituted aryl;
- d) heteroaryl;
- e) substituted heteroaryl;
- f) heterocyclic;
- g) substituted heterocyclic;
- h) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkenyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
- i) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkenyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
- j) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
- and
- k) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
- A is selected from the group consisting of R5, (CO)R5, (CO)OR5, (CO)NHR5, SO2R5, (SO2)OR5 and SO2NHR5;
- R5 is selected from the group consisting of:
- a) hydrogen
- b) aryl;
- c) substituted aryl;
- d) heteroaryl;
- e) substituted heteroaryl;
- f) heterocyclic;
- g) substituted heterocyclic;
- h) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
- i) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
- j) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
- and
- k) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
- B is H or CH3;
- L is selected from the group consisting of:
- (i) hydrogen;
- (ii) aryl;
- (iii) substituted aryl;
- (iv) heteroaryl;
- (v) substituted heteroaryl;
- (vi) heterocyclic;
- (vii) substituted heterocyclic;
- (viii) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
- (ix) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
- (x) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
- (xi) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
- Z1 and Z2 are each fluorine;
- m=0, 1, 2 or 3;
- n=1, 2 or 3 and
- h=1, 2, or 3.
Dependencies are inferred from the claim text.