发明名称 Compounds that are ERK inhibitors
摘要 Disclosed are the ERK inhibitors of formula (1): and the pharmaceutically acceptable salts thereof, wherein: A is a five membered monocyclic heteroaryl ring; and B is a monocyclic heterocycloalkyl ring, or a monocyclic heterocycloalkenyl ring, or a bridged monocyclic heterocycloalkyl ring, or a fused (monocyclic heterocycloalkyl ring) cyclopropyl ring. Also disclosed are methods of treating cancer using the compounds of formula (1).;
申请公布号 US8999966(B2) 申请公布日期 2015.04.07
申请号 US201113881050 申请日期 2011.10.24
申请人 Merck Sharp & Dohme Corp. 发明人 Boga Sobhana Babu;Kelly Joseph M.;Zhu Hugh Y.;Alhassan Abdul-Basit;Yao Xin;Gao Xiaolei;Wang James J-S;Desai Jagdish A.;Gudipati Subrahmanyam;Lo Sie-Mun;Zhu Liang;Cooper Alan B.;Deng Yongqi;Shipps, Jr. Gerald W.
分类号 A61K31/397;A61K31/5377;A61K31/506;A61K31/4545;A61K31/454;A61K31/4523;A61K31/4427;A61K31/4439;A61K31/444;C07D413/14;C07D401/14;C07D403/14;C07D221/00;C07D221/02;C07D211/80;C07D405/14;C07D409/14;C07D417/14;C07D471/04;A61K45/06 主分类号 A61K31/397
代理机构 代理人 Parr Richard S.;Ginkel Laura M.
主权项 1. A compound of formula (1):or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from the group consisting of A is selected from the group consisting of triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, imidazolyl, and imidazolidinyl; B is selected from the group consisting of wherein R3 is selected from the group consisting of: (a) alkyl, (b) aryl, (c) —C(O) —(C1-C6)alkyl, (d) —SR18, (e) —C(O)—(C3-C6)cycloalkyl, (f) —N(R18)2, (g) —NH—C(O) —R18, (h) —NH—S(O)2R18, (i) —C(O) —N(R20)2 and (j) ═O, m is 0 to 3, and n is 1 to 3, and X is selected from the group consisting of —NR5—, O, S, SO, SO2 and C; R4 is selected from the group consisting of: (1) —(C1-C2)alkylene-aryl, (2) —C(O)-aryl, (3) -(C1-C2)alkylene-heteroaryl, (4) —(C1-C2)alkylene-(fused heteroarylaryl), (5) —(C1-C2)alkylene-C(O)-heterocycloalkyl, (6) fused (arylcycloalkyl), (7) —(C1-C2)alkylene-cycloalkyl, (8) —(C1-C2)alkylene-(bridgedheterocycloalkyl), (9) —C(O)—(C1-C2)alkylene-aryl, and (10) —C(O)—(C1-C2)alkylene-aryl; and wherein said R4 groups are optionally substituted with 1 to 5 substitutents independently selected from the group consisting of: (a) alkyl, (b) alkoxy, (c) halo, (d) —O-alkylene-O-alkyl, (e) —O-alkylene-CN, (f) —O-(halo substituted alkyl), (g) —NH2, (h) —O—(C3-C6)cycloalkyl, (i) —S-alkyl, (j) —N(R22)2, (k) —C(O)—(C1-C4)alkyl, (1) —C(O)—N(R18)2, (m) cycloalkyl, (n) —CF3, (o) —CF2, and (p) —CF; and wherein said fused heteroarylaryl moiety of (4) is a fused monocyclic heteroaryl ring fused to an aryl ring, said heterocycloalkyl moiety of (5) is a monocyclic ring, said fused (arylcycloalkyl) in (6) is a monocyclic aryl ring fused to a monocyclic cycloalkyl ring, and said heterocycloalkyl moiety of (8) (not including the bridge) is a monocyclic ring; and provided that when R4 is substituted, and when the alkylene group of said R4 group (1), (3), (4), (5), (7), or (8) is substituted, then the alkylene carbon bound to the nitrogen of the B ring for said R4 groups (1), (3), (4), (5), (7), and (8) is not substituted with a heteroatom; each R5 is independently selected from the group consisting of: (1) H, (2) (C1-C4)alkyl, (3) —C(O)—(C1-C4)alkyl, and (4) —C(O)—N(R18)2; each R6 is independently selected from the group consisting of: (1) alkyl, (2) cycloalkyl, (3) —CF3, (4) —CF2, and (5) —CF; each R8 is independently selected from the group consisting of: (1) H, (2) alkyl, and (3) cycloalkyl; each R10 is independently selected from the group consisting of: (1) alkyl, (2) cycloalkyl, and (3) —N(R18)2; each R12 is independently selected from the group consisting of: (1) alkyl, and (2) cycloalkyl; each R14 is independently selected from the group consisting of: (1) H, (2) alkyl, and (3) cycloalkyl; each R16 is independently selected from the group consisting of: (1) alkyl, and (2) cycloalkyl; each R18 is independently selected from the group consisting of: (1) H, (2) (C1-C4)alkyl, and (3) (C3-C6)cycloalkyl; each R20 is independently selected from the group consisting of: (1) H, and (2) (C1-C4) alkyl; and (3) wherein each R20 can be taken together, along with the nitrogen to which they are bonded, to form a heterocycloalkyl ring, wherein said heterocycloalkyl ring is optionally substituted with 1-2 independently selected halo atoms; and each R22 is independently selected from the group consisting of: alkyl.
地址 Rahway NJ US