发明名称 SELECTIVE GRP94 INHIBITORS AND USES THEREOF
摘要 The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.
申请公布号 US2016194328(A1) 申请公布日期 2016.07.07
申请号 US201414912082 申请日期 2014.08.15
申请人 Memorial Sloan-Kettering Cancer Center 发明人 Chiosis Gabriela;Yan Pengrong;Patel Pallav;Patel Hardik J.;Taldone Tony;Yang Chenghua;Sun Weilin;Ochiana Stefan O.
分类号 C07D473/34;C40B30/02;G01N33/50;C07D519/00 主分类号 C07D473/34
代理机构 代理人
主权项 1. A compound of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein: (a) Y is —C(RY)2—, —S—, —NR—, —O—, (b) each of Z1 and Z3 are independently —CH— or —N—;(c) Z2 is —N— or —CR10—, wherein R10 is H or unsubstituted or substituted —(C1-C6)aliphatic;(d) each of Z4, Z5, Z6, Z7 and Z8 are independently —C— or —N—, with the provisos that at least one of Z4, Z6 and Z7 is —C— and no three consecutive Z4 through Z8 are N;(e) X1 is —H, -halo, —N(R)2, —OR, —CN, or unsubstituted or substituted —(C1-C6)aliphatic;(f) each of X2, X3, X4, X5, and X6 are independently —H, -halo, —SR, —N(R)2, —OR, —CN, —NO2, —CN, —C(O)R, —C(O)2R, —S(O)R, —S(O)2R, —C(O)N(R)2, —SO2N(R)2, —OC(O)R, —N(R)C(O)R, —N(R)SO2R, —OC(O)N(R)2, unsubstituted or substituted —(C1-C6)aliphatic, or an unsubstituted or substituted group selected from (5- or 6-membered)aryl, (5- or 6-membered)arylalkyl, and (5- or 6-membered)heterocyclic aromatic or heterocyclic non-aromatic group; with the provisos that at least one of X2, X4 and X5 is —H and that X2 is absent when Z4 is —N—, X3 is absent when Z5 is —N—, X4 is absent when Z6 is —N— and X5 is absent when Z7 is —N—;(g) R1 is —(C1-C6)aliphatic-N+—(R2)(R3)(R4), —(C1-C6)aliphatic-N—R3R4, —(C1-C6)aliphatic-C(═O)N—R3R4, —(C1-C6)aliphatic-R3R4, —(C1-C6)aliphatic-R2R3R4, —(C1-C6)aliphatic-N—CR2R3R4, —(C1-C6)aliphatic-C(halo)3, —(C1-C6)aliphatic-alkenyl, —(C1-C6)aliphatic-alkynyl, —(C1-C6)aliphatic-(C3-C8)cycloalkyl, —(C1-C6)aliphatic-(C3-C8)heterocyclo, —(C1-C6)aliphatic-phenyl, —(C1-C6)aliphatic-(5 or 6-membered)heteroaryl, —(C1-C6)aliphatic-cyano, where the cyloalkyl, heterocyclo, heteroaryl, or phenyl is unsubstituted or substituted, with the proviso that when all of R2-R4 are present the compound further comprises a pharmaceutically acceptable counter ion;(h) R2 and R3 are independently hydrogen, —N(R)2, —CH2CH(OH)R4, —CH(OH)CH2R4, —CH2SO2NHR4, —CH2NHSO2R4, or unsubstituted or substituted —(C1-C6)aliphatic, or R3 and R4 form an unsubstituted or substituted 3- to 7-membered heterocyclic ring when taken together with the nitrogen to which they are attached;(i) R4 is hydrogen, halogen, or unsubstituted or substituted —(C1-C6)aliphatic;(j) each RY is independently R, —OR, or halo;(k) Z3 can be cyclized with X2 to form a cyclic aryl, heteroaryl, alkyl or heteroalkyl ring; and(l) each R is independently hydrogen, unsubstituted C1-6 aliphatic, or C1-6 aliphatic substituted with halo, —OH, —CN, or —NH2; wherein each substituted group is substituted with one or more groups selected from halo, —N(R)2, —OR, —CN, oxo, unsubstituted C1-6 aliphatic, or C1-6 aliphatic substituted with halo, —OH, —CN, or —NH2.
地址 New York NY US