发明名称 HCV protease inhibitors and uses thereof
摘要 The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
申请公布号 US8778877(B2) 申请公布日期 2014.07.15
申请号 US200812339770 申请日期 2008.12.19
申请人 Celgene Avilomics Research, Inc. 发明人 Niu Deqiang;Petter Russell C.;Singh Juswinder;Kluge Arthur F.;Qiao Lixin
分类号 A61K38/00;C07K5/078;C07K5/083;C07K5/087;C07K5/08 主分类号 A61K38/00
代理机构 Choate, Hall & Stewart, LLP 代理人 Choate, Hall & Stewart, LLP ;Reid Andrea L. C.;Rearick John P.
主权项 1. A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: R1 and R1′ are independently hydrogen or optionally substituted C1-6 aliphatic, or R1 and R1′ are taken together to form an optionally substituted 3-7 membered carbocyclic ring; R2a is —OH or —NHSO2R2; R2 is —N(R)2 or an optionally substituted group selected from C3-7 cycloalkyl, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R is independently hydrogen, optionally substituted C1-6 aliphatic, or: two R on the same nitrogen atom are taken together with the nitrogen to form a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R3 is a warhead -L-Y, 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)—; andZ is hydrogen or C1-6 aliphatic substituted with oxo, halogen, NO2, or CN; or R3 and R1 are taken together with their intervening atoms to form an optionally substituted saturated or unsaturated 12-18 membered ring having 2-6 heteroatoms independently selected from nitrogen oxygen, or sulfur, wherein the ring formed thereby comprises a warhead group -L-Y; or R3 and a ring formed by R1 and R1′ are taken together with their intervening atoms to form an optionally substituted saturated or unsaturated 12-18 membered ring having 2-6 heteroatoms independently selected from nitrogen oxygen, or sulfur, wherein the ring formed thereby comprises a warhead group -L-Y; R4 is H, —NHC(O)R5, —NHC(O)OR6,or a natural or unnatural amino acid side-chain group; each R5 is independently —N(R)2 or an optionally substituted group selected from C1-6 aliphatic, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R6 is an optionally substituted group selected from C1-6 aliphatic, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and R7 is an optionally substituted group selected from C1-6 aliphatic, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and Rz is  or R4 and Rz are taken together with their intervening atoms to form a saturated or unsaturated 16-22 membered ring having 2-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein the 16-22 membered ring is optionally substituted with (Rm)p, wherein: p is an integer from 1 to 6, inclusive;each occurrence of Rm is independently halogen, —ORo; —CN; —N(Ro)2; or an optionally substituted group selected from C1-6 aliphatic or C3-7 cycloalkyl; andeach Ro is independently optionally substituted C1-6 aliphatic; each occurrence of Ry is independently selected from halogen, —ORo, —CN, —NO2, —N(Ro)2, or optionally substituted C1-4 aliphatic; m is an integer from 0 to 4, inclusive; s is an integer from 0 to 4, inclusive; and t is an integer from 0 to 4, inclusive; wherein the sum of s and t is non-zero.
地址 Bedford MA US