发明名称 Bicyclic heterocyclic compounds as FGFR inhibitors
摘要 The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
申请公布号 US8895745(B2) 申请公布日期 2014.11.25
申请号 US200712520481 申请日期 2007.12.21
申请人 Astex Therapeutics Limited 发明人 Berdini Valerio;Besong Gilbert Ebai;Callaghan Owen;Carr Maria Grazia;Congreve Miles Stuart;Gill Adrian Liam;Griffiths-Jones Charlotte Mary;Madin Andrew;Murray Christopher William;Nijjar Rajdeep Kaur;O'Brien Michael Alistair;Pike Andrew;Saxty Gordon;Taylor Richard David;Vickerstaffe Emma
分类号 C07D471/04;A61K31/437;C07D487/04 主分类号 C07D471/04
代理机构 Heslin Rothenberg Farley & Mesiti P.C. 代理人 Heslin Rothenberg Farley & Mesiti P.C.
主权项 1. A compound of formula (Id): wherein J and L are independently selected from carbon and nitrogen; R5 represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, alkanol, C1-6 alkanol, haloC1-6 alkyl, —(CH2)n—NRxRy, —(CH2)s—COORz, or —(CH2)n—O—(CH2)m—OH, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups may be optionally substituted by one or more Ra groups; Rx, Ry and Rz independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkanol, —COOC1-6 alkyl, hydroxy, C1-6 alkoxy, haloC1-6 alkyl, —CO—(CH2)n—C1-6 alkoxy, C1-6 alkylamino, C3-8 cycloalkyl or C3-8 cycloalkenyl; R2 and R6 independently represent halogen, hydrogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —C≡N, C3-8 cycloalkyl, C3-8 cycloalkenyl, —NHSO2Rw, —CH═N—ORw, an aryl or heterocyclyl group wherein said aryl and heterocyclyl groups may be optionally substituted by one or more Rb groups, and said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl may be optionally substituted by one or more Rb′ groups, provided that R2 and R6 do not both represent hydrogen; Rw represents hydrogen or C1-6 alkyl; Ra represents halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, —ORx, —(CH2)n—O—C1-6 alkyl, —O—(CH2)n—ORx, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkanol, ═O, ═S, nitro, Si(Rx)4, —(CH2)s—CN, —SO—Rx, —SO2—Rx, —CORx, —(CRxRy)s—COORz, —(CH2)s—CONRXRy, —(CH2)s—NRxRy, —(CH2)s—NRxCORy, —(CH2)s—NRxSO2—Ry, —(CH2)s—NH—SO2—NRxRy, —OCONRxRy, —(CH2)s—NRxCO2Ry, —O—(CH2)s—CRxRy—(CH2)t—ORz or —(CH2)s—SO2NRxRy groups; q represents an integer from 0 to 3; Rb represents an Ra group or a —Y-carbocyclyl or —Z-heterocyclyl group wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more Ra groups; Y and Z independently represent a bond, —CO—(CH2)s—, —COO—, —(CH2)n—, —NRx—(CH2)n—, —(CH2)n—NRx—, —CONRx—, —NRxCO—, —SO2NRx—, —NRxSO2—, —NRxCONRy—, —NRxCSNRy—, —O—(CH2)s—, —(CH2)s—O—, S—, —SO— or —(CH2)s—SO2—; Rb′ represents an Ra′ group or a —Y-carbocyclyl or —Z-heterocyclyl group wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more Ra groups; Ra′ represents halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, —(CH2)n—O—C1-6 alkyl, —O—(CH2)n—ORx, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkanol, ═S, nitro, Si(Rx)4, —(CH2)s—CN, —S—Rx, —SO—Rx, —SO2—Rx, —CORx, —(CRxRy)s—COORz, —(CH2)s—CONRxRy, —(CH2)s—NRxRy, —(CH2)s—NRxCORy, —(CH2)s—NRxSO2—Ry, —(CH2)s—NH—SO2—NRxRy, —OCONRxRy, —(CH2)s—NRxCO2Ry, —O—(CH2)s—CRxRy—(CH2)t—ORz or —(CH2)s—SO2NRxRy groups; m and n independently represent an integer from 1-4; s and t independently represent an integer from 0-4; or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound of formula (Id) is not: N-{2-fluoro-4-[6-(1-trityl-1H-4-pyrazolyl)imidazo[1,2-a]pyridine-3-yl]phenyl}-N′-isopropyl urea; or N-{2-fluoro-4-[6-(1H-4-pyrazolyl)imidazo[1,2-a]pyridin-3-yl]phenyl}-N′-isopropylurea.
地址 Cambridge GB