发明名称 Inhibitors of histone deacetylase
摘要 This invention comprises the novel compounds of formula (I); wherein n, R1, R2, R3, R4, Q, X, Y, Z and ; have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.
申请公布号 US9150560(B2) 申请公布日期 2015.10.06
申请号 US201414186343 申请日期 2014.02.21
申请人 Janssen Pharmaceutica NV 发明人 Van Emelen Kristof;Verdonck Marc Gustaaf Celine;Van Brandt Sven Franciscus Anna;Angibaud Patrick Rene;Meerpoel Lieven;Dyatkin Alexey Borisovich
分类号 C07D207/14;A61K31/40;C07D413/12;C07D211/14;C07D207/09;C07D211/58;C07D213/78;C07D217/02;C07D239/42;C07D295/155;C07D295/26;C07D307/68;C07D401/04;C07D401/12;C07D403/04;C07D409/12;C07D413/04;C07D471/04;C07D513/04;C12Q1/48;A61K31/435;A61K31/495;A61K31/506;A61K45/06;A61K31/4427;A61K31/454;A61K31/5377;A61K31/55;A61K31/472;A61K31/496;C07D217/16;C07D405/06;A61K31/4545;C07D403/12;C12Q1/34;C07D471/10 主分类号 C07D207/14
代理机构 Baker & Hostetler LLP 代理人 Baker & Hostetler LLP
主权项 1. A compound of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein n is 0 or 1 and when n is 0 then a direct bond is intended; Q is X is Y is Z is R1 is —C(O)NR5R6, —N(H)C(O)R7, —C(O)—C1-6alkanediylSR7, —NR8C(O)N(OH)R7, —NR8C(O)C1-6alkanediylSR7, or —NR8C(O)C═N(OH)R7 wherein R5 and R6 are each independently selected from hydrogen, hydroxy, C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl or aminoaryl; R7 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, arylC1-6alkyl, C1-6alkylpyrazinyl, pyridinone, pyrrolidinone or methylimidazolyl; R8 is hydrogen or C1-6alkyl; R2 is hydrogen, halo, hydroxy, amino, nitro, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, di(C1-6alkyl)amino, hydroxyamino or naphtalenylsulfonylpyrazinyl; R3 is arylC2-6alkenediyl, furanylcarbonyl, naphthalenylcarbonyl, —C(O)phenylR9, C1-6alkylaminocarbonyl, aminosulfonyl, arylaminosulfonyl, aminosulfonylamino, di(C1-6alkyl)aminosulfonylamino, arylaminosulfonylamino, aminosulfonylaminoC1-6alkyl, di(C1-6alkyl)aminosulfonylaminoC1-6alkyl, arylaminosulfonylaminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, C1-12 alkylsulfonyl, di(C1-6alkyl)aminosulfonyl, trihaloC1-6alkylsulfonyl, di(aryl)C1-6alkylcarbonyl, thiophenylC1-6alkylcarbonyl, pyridinylcarbonyl or arylC1-6alkylcarbonyl; wherein each R9 is independently selected from phenyl; phenyl substituted with one, two or three substituents independently selected from halo, amino, C1-6alkyl, C1-6alkyloxy, hydroxyC1-4alkyl, hydroxyC1-4alkyloxy, aminoC1-4alkyloxy, di(C1-4alkyl)aminoC1-4alkyloxy, di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl(C1-6alkyl)aminoC1-6alkyl, hydroxyC1-4alkylpiperazinylC1-4alkyl, C1-4alkyloxypiperidinylC1-4alkyl, hydroxyC1-4alkyloxyC1-4alkylpiperazinyl, C1-4alkylpiperazinylC1-4alkyl, di(hydroxyC1-4alkyl)aminoC1-4alkyl, pyrrolidinylC1-4alkyloxy, morpholinylC1-4alkyloxy, or morpholinylC1-4alkyl; thiophenyl; or thiophenyl substituted with di(C1-4alkyl)aminoC1-4alkyloxy, di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl(C1-6alkyl)aminoC1-6alkyl, pyrrolidinylC1-4alkyloxy, C1-4alkylpiperazinylC1-4alkyl, di(hydroxyC1-4alkyl)aminoC1-4alkyl, or morpholinylC1-4alkyloxy; R4 is hydrogen, hydroxy, amino, hydroxyC1-6alkyl, C1-6alkyl, C1-6alkyloxy, arylC1-6alkyl, aminocarbonyl, hydroxycarbonyl, aminoC1-6alkyl, aminocarbonylC1-6alkyl, hydroxycarbonylC1-6alkyl, hydroxyaminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylaminoC1-6alkyl or di(C1-6alkyl)aminoC1-6alkyl; aryl in the above is phenyl, or phenyl substituted with one or more substituents each independently selected from halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, cyano or hydroxycarbonyl.
地址 Beerse BE
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