发明名称 Substituted quinoxaline DNA-PK inhibitors
摘要 The compounds represented by Formula (I) and pharmaceutically acceptable salts thereof are useful as inhibitors of DNA-PK:; where each of R1, R2, X, Ring A, Ring B and Ring C is as described herein. Pharmaceutically acceptable compositions comprise said compounds. These compounds and pharmaceutical compositions are used in the treatment of various disease, conditions, or disorders.
申请公布号 US9340557(B2) 申请公布日期 2016.05.17
申请号 US201414205657 申请日期 2014.03.12
申请人 Vertex Pharmaceuticals Incorporated 发明人 Maxwell John Patrick;Charifson Paul S.;Tang Qing;Ronkin Steven M.;Jackson Katrina Lee;Pierce Albert Charles;Lauffer David J.;Li Pan;Giroux Simon;Xu Jinwang;Cottrell Kevin M.;Morris Mark A.;Waal Nathan D.;Court John J.;Gu Wenxin;Deng Hongbo
分类号 A61K31/498;C07D241/44;C07D513/04;A61K31/506;A61K31/5377;A61K31/5386;C07D241/40;C07D401/14;C07D403/12;C07D403/14;C07D405/12;C07D405/14;C07D413/12;C07D417/12;C07D471/04;C07D473/40;C07D475/00;C07D487/04;C07D491/048;C07D498/08;C07D241/42;C07D413/04;C07D491/052 主分类号 A61K31/498
代理机构 Wolf, Greenfield & Sacks, P.C. 代理人 Wolf, Greenfield & Sacks, P.C.
主权项 1. A compound represented by Formula (I) or a pharmaceutically acceptable salt thereof:wherein Ring A is a ring system selected from Ring B is a ring system selected from  wherein Ring B is optionally substituted with up to 4 fluorine atoms, up to two OH or up to two C1-4alkyl which is optionally substituted with up to 3 fluorine atoms, up to two OH, or up to two OC1-2alkyl groups; Ring C is a cyclobutane ring; X is —NH—, —O—, or —OC1-4 alkyl-; each of R1 and R2 is, independently, hydrogen, —C(O)NHR4, —C(O)OR4, —NHC(O)R4, —NHC(O)OR4, —NHC(O)NHR4, —NHS(O)2R4, —C0-4 alkyl-NHR4, or —OR4, wherein R1 and R2 cannot simultaneously be hydrogen, and wherein R1 and R2 and the intervening carbon atom can form a dioxane or dioxolane ring; R3 is hydrogen, —C1-4alkyl, fluoro, chloro, —OC1-2alkyl, —C(O)H, —C(O)OH, —C(O)OC1-2alkyl, -CN, —C(O)NHC1-2alkyl, or —C(O)NH2, wherein each of said R3 alkyl is optionally substituted with up to 3 fluorine atoms, up to two OH, or up to two OC1-2alkyl groups; R4 is hydrogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-5cycloalkyl, phenyl, a 5-10-membered monocyclic or bicyclic heteroaryl ring selected from pyrrole, imidazole, pyrazole, triazole, thiazole, isothiazole, oxazole, pyridine, pyrimidine, pyrimidinone, pyrazine, pyridazine, or quinoline, or a 4-10-membered monocyclic or bicyclic heterocyclyl ring selected from oxetane, tetrahydrofuran, tetrahydropyran, dihydroisoxazole, pyrimidine-2,4(1H,3H)-dione, dihydrofuropyrimidine, dihydropyranopyrimidine, dihydropyrrolopyrimidine, tetrahydropteridine, or tetrahydropyridopyrimidine, wherein each of said R4 groups is optionally substituted with up to four Br, Cl, F, or C1-4alkyl, up to three CN, NO2, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, C0-4 alkyl-C3-5 cycloalkyl, C0-4 alkyl-O—C1-4 alkyl, C0-4 alkyl-O—C0-4 alkyl-C3-5 cycloalkyl, C(O)OC1-4 alkyl, C(O)OC0-4 alkyl-C3-5 cycloalkyl, C0-4 alkyl-C(O)NH2, C(O)NHC1-4 alkyl, C(O)N(C1-4alkyl)2, C(O)NH(C0-4 alkyl-C3-5 cycloalkyl), CH2OR5, C0-4 alkyl-C(O)R5, C0-4 alkyl-C(O)N(R5)2, C0-4 alkyl-C(O)OR5, C0-4 alkyl-NHC(O)R5, C0-4 alkyl-N(R5)2, a heterocyclic ring system selected from oxetane, azetidine, tetrahydrofuran, dihydropyran, tetrahydropyran, morpholine, piperidine, pyrrolidine or piperazine, a heteroaryl ring system selected from furan, oxazole, oxadiazole, pyrrole, pyrazole, triazole, oxadiazole or tetrazole, or up to two OR5, wherein each of said optional R4 substituents is optionally substituted with up to four fluorine atoms, up to two C1-4alkyl groups, up to two OH groups, up to two OC1-4alkyl groups, up to two SC1-4alkyl groups, a C(O)C1-4 alkyl, a C(O)OC1-4 alkyl, or a C(O)OC0-4 alkyl-C3-5 cycloalkyl; and each R5 is, independently, hydrogen, C1-4alkyl, a 5-6-membered heteroaryl selected from imidazole, triazole, thiazole, pyridine, or pyrimidine, a 4-6-membered heterocyclyl selected from oxoetane, tetrahydrofuran, or tetrahydropyran, and each R5 group is optionally substituted with chloro, up to three fluorine atoms, up to two C1-2alkyl, CH2OH, CN, up to two OH, up to two OC1-2alkyl, a spirooxetane, pyrrolidine, or triazole, or two R5 groups together with the intervening nitrogen atom form a morpholine ring, azetidine ring, pyrrolidine ring, piperidine ring, or piperazine ring.
地址 Boston MA US