发明名称 Heterocyclic compounds as ERK inhibitors
摘要 The present invention provides a compound of the Formula I: (Formular I should be inserted here) or a pharmaceutically acceptable salt, solvate or ester thereof, wherein R, R1, R2 and R3 are as defined herein. The compounds are ERK inhibitors. Also disclosed are pharmaceutical compositions comprising the above compounds and methods of treating cancer using the same.;
申请公布号 US8999957(B2) 申请公布日期 2015.04.07
申请号 US201113703250 申请日期 2011.06.22
申请人 Merck Sharp & Dohme Corp. 发明人 Deng Yongqi;Zhu Liang;Shipps, Jr. Gerald W.;Lo Sie-Mun;Sun Binyuan;Huang Xiaohua;Bienstock Corey;Cooper Alan B.;Gao Xiaolei;Yao Xin;Zhu Hugh Y.;Kelly Joseph M.;Boga Sobhana Babu;Alhassan Abdul-Basit;Tagat Jayaram R.;Mansoor Umar Faruk;Wilson Kevin J.;O'Boyle Brendan M.;Daniels Matthew Hersh;Schell Adam;Siliphaivanh Phieng;Fischer Christian
分类号 C07D401/12;C07D409/14;C07D413/14;C07D417/14;C07D471/04;C07D401/14;C07D405/14;A61K31/454;A61K31/4545;A61K31/506;A61K31/5377;A61K31/55;A61K31/551;A61K31/695;A61K45/06;C07F7/18 主分类号 C07D401/12
代理机构 代理人 Parr Richard S.;Ginkel Laura M.
主权项 1. A compound of Formula Ior a pharmaceutically acceptable salt thereof, wherein: R is selected from the group consisting of: H, alkyl and hydroxylalkyl; R1 is selected from the group consisting of heterocyclyl, heterocycloalkenyl, aryl and heteroaryl, wherein when said heterocyclyl, heterocycloalkenyl, aryl or heteroaryl has two substituents on adjacent ring atoms, said substituents together with the ring atoms to which they are attached, optionally form a five- or six-membered heterocyclyl, aryl or heteroaryl; R2 is H or alkyl; R3′ is selected from the group consisting of: each R3 independently is selected from the group consisting of —C(═O)—O-alkyl, halo, haloalkyl, —OSi(alkyl)3, —C(═O)—OH, —C(O)NRBRC—C(O)NH-alkyl-NRDRE, —C(O)NH-alkyl-O-alkyl-aryl, —C(O)RF, —C(O)NH—NHRG, —C(O)NH—Oalkyl, —C(O)NH—O-alkyl-cycloalkyl, alkyl, hydroxyl, alkoxy, alkenyl, cycloalkyl, cycloalkenyl, alkynyl, heterocyclyl, heterocyclenyl, aryl, and heteroaryl; or wherein two R3 groups together with the carbon atom to which both R3 groups are attached form —C(═O)—; RB and RC are each independently selected from the group consisting of: H, alkyl, cycloalkyl, cycloalkylalkyl-, heteroaryl, aryl, heterocycloalkyl, benzyl, and alkoxy, wherein said alkyl, cycloalkyl, cycloalkylalkyl-, heteroaryl, aryl, heterocycloalkyl, benzyl, and alkoxy groups are optionally substituted with 1 to 3 substitutents independently selected from the group consisting of: —OH, alkyl, alkoxy, hydroxyalkyl-, halo, and —C(O)Oalkyl; RD and RE are each independently selected from the group consisting of: H, alkyl, and —C(O)Oalkyl; RF is a heterocycloalkyl optionally substituted with 1-3 substitutents independently selected from the group consisting of: —OH, halo, —C(O)Oalkyl, —C(O)NH-alkyl, —C(O)alkyl, alkyl, —C(O)Ocycloalkyl, —O—Si(alkyl)2 (wherein each alkyl is independently selected), and —C(O)Oheterocycloalkyl; RG is selected from the group consisting of: H, alkyl, and —C(═S)—NH-alkyl; each m independently is 0, 1, 2 or 3; n independently is 1; Each R4 is independently selected from the group consisting of: H, alkyl, cycloalkyl, aryl, heteroaryl, —SO2-aryl, —C(O)—O-alkyl, —C(O)—O-alkylaryl, and —(CR5R6)pR7, wherein p is 1 or 2; wherein when said R4 cycloalkyl has two substituents on adjacent carbon atoms, said substituents together with the carbon atoms to which they are attached, optionally form a five- or six-membered ring selected from the group consisting of heterocyclyl, aryl and heteroaryl; R4′ is selected from the group consisting of H and alkyl; Ra is alkyl; R5 and R6 independently are selected from the group consisting of H, D, halo, —OH, —C(O)NRHR2, —C(O)—O-alkyl, and alkyl; or wherein one —CR5R6— is —C(═O)—; RH is selected from the group consisting of H and alkyl; and R7 is selected from the group consisting of H, —O-alkyl-aryl, aryl and heteroaryl, wherein when said aryl or heteroaryl has two substituents on adjacent carbon atoms, said substituents together with the carbon atoms to which they are attached, optionally form a five- or six-membered ring selected from the group consisting of cycloalkylheterocyclyl, aryl or heteroaryl.
地址 Rahway NJ US