发明名称 DNA-PK inhibitors
摘要 The present invention relates to compounds useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
申请公布号 US9359380(B2) 申请公布日期 2016.06.07
申请号 US201414205508 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 C07D513/04;C07D498/00;C07D241/40;C07D405/12;C07D471/04;C07D417/12;C07D413/12;A61K31/506;A61K31/5377;A61K31/5386;C07D401/14;C07D403/12;C07D403/14;C07D405/14;C07D473/40;C07D475/00;C07D487/04;C07D491/048;C07D498/08;C07D241/42;C07D413/04;C07D241/44;C07D491/052 主分类号 C07D513/04
代理机构 Wolf, Greenfield & Sacks, P.C. 代理人 Wolf, Greenfield & Sacks, P.C.
主权项 1. A compound having the formula: 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 or up to two C1-4alkyl optionally substituted with up to 3 fluorine atoms, up to two OH, or up to two OC1-2alkyl groups; X is NH or O; 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, —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, C1-4 alkyl, fluoro, chloro, OC1-2alkyl, C(O)OH, C(O)OC1-2 alkyl, 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 Br, Cl, up to three fluorine atoms, up to three C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl, an oxetane ring, a tetrahydrofuran ring, a dihydropyran ring, a tetrahydropyran ring, a pyrrolidine ring, a pyrazole ring, a triazole ring, a tetrazole ring, an oxadiazole ring, CN, CH2OR5, C(O)R5, C(O)N(R5)2, C(O)OR5, NO2, NHC(O)R5, N(R5)2, or up to two OR5, wherein each of said optional R4 substituents is optionally substituted with up to 3 fluorine atoms, up to two C1-4alkyl groups, up to two OH groups, up to two OC1-4alkyl groups, or up to two SC1-4alkyl groups; 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 oxetane, 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, wherein each of said rings is optionally substituted with up to 3 fluorine atoms, up to two OH, or up to two OC1-2alkyl groups.
地址 Boston MA US