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US 2015/0031106 A1Published application
Hcv protease inhibitors and uses thereof
AssigneeCelgene Avilomics Research, Inc.
InventorsDeqiang Niu, Russell C. Petter, Juswinder Singh, Arthur F. Kluge, Lixin Qiao
Life of this patent
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Abstract
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
Claims19
1-47. (canceled)
A conjugate of the formula:
- Cys159-linker-inhibitor moiety,
- wherein:
- the Cys159 is Cys159 of HCV protease;
- the inhibitor moiety is a moiety that selectively binds HCV protease;
- the linker is a bivalent group resulting from the reaction of Cys159 of HCV protease with a L-Y warhead group, wherein
- L is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and one or two methylene units of L are independently replaced by —NRC(O)—, —C(O)NR—, —N(R)SO2—, —SO2N(R)—, —S—, —S(O)—, —SO2—, —OC(O)—, —C(O)O—, cyclopropylene, —O—, —N(R)—, or —C(O)—;
- Y is hydrogen, C1-6 aliphatic optionally substituted with oxo, halogen, NO2, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 Re groups;
- and
- each Re is independently selected from -Q-Z, oxo, NO2, halogen, CN, a suitable leaving group selected from alkoxy, sulphonyloxy, optionally substituted alkylsulphonyloxy, optionally substituted alkenylsulfonyloxy, optionally substituted arylsulfonyloxy, acyl, diazonium, or C1-6 aliphatic substituted with oxo, halogen, NO2, or CN, wherein:
- Q is a bivalent C1-6 unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —SO—, or —SO2—, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO2—, or —SO2N(R)—;
- and
- Z is hydrogen or C1-6 aliphatic substituted with oxo, halogen, NO2, or CN.
9 more elements
A conjugate of the formula:
- Cys159-linker-inhibitor moiety, wherein:
- the Cys159 is Cys159 of HCV protease;
- the inhibitor moiety is a moiety that selectively binds HCV protease;
- the linker is a bivalent group resulting from the reaction of Cys159 of HCV protease with a L-Y warhead group, wherein
- L-Y is selected from the group consisting of:
2 more elements
A conjugate of the formula:
- Cys16-linker-inhibitor moiety, wherein:
- the Cys16 is Cys16 of HCV protease;
- the inhibitor moiety is a moiety that selectively binds HCV protease;
- the linker is a bivalent group resulting from the reaction of Cys16 of HCV protease with a L-Y warhead group, wherein
- L is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and one or two methylene units of L are independently replaced by —NRC(O)—, —C(O)NR—, —N(R)SO2—, —SO2N(R)—, —S—, —S(O)—, —SO2—, —OC(O)—, —C(O)O—, cyclopropylene, —O—, —N(R)—, or —C(O)—;
- Y is hydrogen, C1-6 aliphatic optionally substituted with oxo, halogen, NO2, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 Re groups;
- and
- each Re is independently selected from -Q-Z, oxo, NO2, halogen, CN, a suitable leaving group selected from alkoxy, sulphonyloxy, optionally substituted alkylsulphonyloxy, optionally substituted alkenylsulfonyloxy, optionally substituted arylsulfonyloxy, acyl, diazonium, or C1-6 aliphatic substituted with oxo, halogen, NO2, or CN, wherein:
- Q is a bivalent C1-6 unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —SO—, or —SO2—, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO2—, or —SO2N(R)—;
- and
- Z is hydrogen or C1-6 aliphatic substituted with oxo, halogen, NO2, or CN.
8 more elements
A conjugate of the formula:
- Cys16-linker-inhibitor moiety, wherein:
- the Cys16 is Cys16 of HCV protease;
- the inhibitor moiety is a moiety that selectively binds HCV protease;
- the linker is a bivalent group resulting from the reaction of Cys16 of HCV protease with a L-Y warhead group, wherein
- L-Y is selected from the group consisting of:
2 more elements
Dependencies are inferred from the claim text.