发明名称 Compounds and their methods of use
摘要 Compounds and compositions comprising compounds that inhibit glutaminase are described herein. Also described herein are methods of using the compounds that inhibit glutaminase in the treatment of cancer.
申请公布号 US9029531(B2) 申请公布日期 2015.05.12
申请号 US201314086003 申请日期 2013.11.21
申请人 Agios Pharmaceuticals, Inc. 发明人 Lemieux Rene M.;Popovici-Muller Janeta;Salituro Francesco G.;Saunders Jeffrey O.;Travins Jeremy;Chen Yongsheng
分类号 C07D401/00;C07D403/00;C07D417/14;C07D285/135 主分类号 C07D401/00
代理机构 Lando & Anastasi LLP 代理人 Lando & Anastasi LLP
主权项 1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein X is C3-C7 cycloalkylene; each W, Y and Z is independently —S—, —CH═, —O—, —N═, or —NH—, provided that at least one of W, Y and Z is not —CH═; each R1 and R2 is independently —NH2, —N(R3)—C(O)—R4, —C(O)—N(R3)—R4, —N(R3)—C(O)—O—R4, —N(R3)—C(O)—N(R3)—R4 or —N(R3)—C(O)—SR4; each R3 is independently hydrogen, C1-6 alkyl or aryl; each R4 is independently C1-6 alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl, cycloalkylalkyl, heterocyclylalkyl, or heterocyclyl, each of which is substituted with 0-3 occurrences of R5; each R5 is independently C1-6 alkyl, C1-6 alkoxy, —O—C1-6 alkyleneC1-6 alkoxy, C1-6 thioalkoxy, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl, heterocyclyl, cyano, halo, oxo, —OH, —OCF3, —OCHF2, —SO2—C1-6 alkyl, —NO2, —N(R7)—C(O)—C1-6 alkyl, —C(O)N(R7)2, —N(R7)S(O)1-2—C1-6 alkyl, —S(O)2N(R7)2, —N(R7)2, —C1-6 alkylene-N(R7)2, wherein said alkyl, C1-6 alkoxy, —O—C1-6 alkyleneC1-6 alkoxy, C1-6 thioalkoxy, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl, heterocyclyl, —SO2—C1-6 alkyl, —NO2, —N(R7)—C(O)—C1-6 alkyl, —C(O)N(R7)2, —N(R7)S(O)1-2—C1-6 alkyl, —S(O)2N(R7)2, —N(R7)2, or —C1-6 alkylene-N(R7)2 is optionally substituted with 0-3 occurrences of R8; or two adjacent R5 moieties, taken together with the atoms to which they are attached form a cycloalkyl or heterocyclyl; each R6 is independently hydrogen, fluoro, C1-6 alkyl, —OH, —NH2, —NH(CH3), —N(CH3)2, or C1-6 alkoxy; each R7 is independently hydrogen or C1-6 alkyl; each R8 is independently halo, C1-6 alkyl, C1-6 haloalkyl, —OH, —N(R7)2, or C1-6 alkoxy, —O—C1-6 alkyleneC1-6 alkoxy, CN, NO2, —N(R7)—C(O)—C1-6 alkyl, —C(O)N(R7)2, —N(R7)S(O)1-2C1-6 alkyl, or —S(O)2N(R7)2; m is 0, 1, or 2; n is 0, 1, or 2; o is 1, 2 or 3; and p is 1, 2 or 3; provided that (1) when X is unsubstituted cyclopropyl, R1 and R2 are not both NH-phenyl; and (2) X is other than substituted cyclobutyl or substituted cyclopentyl.
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