发明名称 Pyrrolidinones as MetAP-2 inhibitors
摘要 Compounds of the formula I in which R1, R2, R3 and R4 have the meanings indicated in Claim 1, are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumors.
申请公布号 US8895535(B2) 申请公布日期 2014.11.25
申请号 US201113878574 申请日期 2011.09.14
申请人 Merck Patent GmbH 发明人 Heinrich Timo;Zenke Frank;Calderini Michel;Musil Djordje
分类号 C07D401/14;C07D409/12;C07D413/12;C07D401/10;C07F5/02;A61K31/4025;A61K31/422;A61K31/433;A61K31/4709;A61K31/5377;A61K31/69;A61K45/06;C07D405/12;C07D403/04;C07D417/12;C07D405/14;A61K31/4245;C07D401/04;A61K31/4439;C07D403/12;C07D207/277;C07D401/12;C07D413/10;C07D401/06;C07D405/04 主分类号 C07D401/14
代理机构 Millen, White, Zelano & Branigan, P.C. 代理人 Millen, White, Zelano & Branigan, P.C.
主权项 1. A compound of formula I in which R1 denotes [C(R4)2]nAr1, (CH2)nHet, (CH2)nCyc,or A, R2 denotes [C(R4)2]nAr2, CH[B(OH)2]CH2Het,(CH2)nHet, (CH2)nCyc, CH(C≡CH)phenyl or A, R3 denotes OH, Hal, NH2, CN, CF3, CHF2 or N3, R4 denotes H or alkyl having 1, 2, 3 or 4 C atoms, or R2 and R4 together denote alkylene having 2, 3, 4 or 5 C atoms, where one CH2 group is optionally replaced by NH, NA, N—COA, N—(CH2)nAr3, N—(CH2)nHet2, CH-A, CH—O—(CH2)nAr3, N—SO2A or O and/or is optionally substituted by A, Ar1 denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH, COOA, CONH2, CONHA, CONA2, NHCOA, NHSO2A, COA, CHO, Het1, SO2NH2 and/or SO2A, Ar2 denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH, COOA, CONH2, CONHA, CONA2, NHCOA, NHSO2A, COA, CHO, Het1, SO2NH2 and/or SO2A, Ar3 denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal, OH, OA and/or A, Het denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, and/or O and/or S atoms which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH, COOA, (CH2)nCONH2, (CH2)nCONHA, (CH2)nCONA2, NHCOA, NHSO2A, COA, CHO, Het1, SO2NH2, SO2A and/or ═O, Het1 denotes a monocyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, and/or O and/or S atoms which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH and/or COOA, Het2 denotes pyridyl, pyrimidinyl, furyl, thienyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl or thiadiazole, A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7 H atoms are optionally replaced by F, Cl, Br, OH, CHO, COA, COOA, CN, CONA2, CONHA and/or CONH2, and/or in which one or two non-adjacent CH and/or CH2 groups are optionally replaced by O, N and/or NR4, or Cyc, Cyc denotes cyclic alkyl having 3-7 C atoms, Hal denotes F, Cl, Br or I, n denotes 0, 1, 2, 3 or 4, or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
地址 Darmstadt DE