发明名称 Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy
摘要 The present invention relates to isoindoline derivatives of the formula (I); or a physiologically tolerated salt thereof. ;The present invention also relates to pharmaceutical compositions comprising such isoindoline derivatives, and the use of such isoindoline derivatives for therapeutic purposes.
申请公布号 US9365512(B2) 申请公布日期 2016.06.14
申请号 US201313764454 申请日期 2013.02.11
申请人 AbbVie Deutschland GmbH & Co. KG;AbbVie Inc. 发明人 Amberg Wilhelm;Lange Udo;Ochse Michael;Pohlki Frauke;Hutchins Charles W.;Zanze Irini;Zhao Hongyu H.;Li Huan-Qiu;Wang Ying X.
分类号 C07D403/12;C07D209/46;C07D405/14;C07D209/44 主分类号 C07D403/12
代理机构 Michael Best & Friedrich LLP 代理人 Mueller Lisa V.;Michael Best & Friedrich LLP
主权项 1. An isoindoline derivative of formula (I) wherein R is R1-W-A1-Q-Y-A2-X1- or —CN; R1 is hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, tri-(C1-C4-alkyl)-silyl-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-alkylcarbonylamino-C1-C4-alkyl, C1-C6-alkyloxycarbonylamino-C1-C4-alkyl, C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, di-C1-C6-alkylaminocarbonylamino-C1-C4 alkyl, C1-C6-alkylsulfonylamino-C1-C4-alkyl, (optionally substituted C6-C12-aryl-C1-C6-alkyl)amino-C1-C4-alkyl, optionally substituted C6-C12-aryl-C1-C4-alkyl, optionally substituted C3-C12-heterocyclyl-C1-C4-alkyl, C3-C12-cycloalkyl, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, halogenated C1-C6-alkoxycarbonyl, C6-C12-aryloxycarbonyl, aminocarbonyl, C1-C6-alkylaminocarbonyl, (halogenated C1-C4-alkyl)aminocarbonyl, C6-C12-arylaminocarbonyl, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, amino-C1-C4-alkoxy, C1-C6-alkylamino-C1-C4-alkoxy, di-C1-C6-alkylamino-C1-C4-alkoxy, C1-C6-alkylcarbonylamino-C1-C4-alkoxy, C6-C12-arylcarbonylamino-C1-C4-alkoxy, C1-C6-alkoxycarbonylamino-C1-C4-alkoxy, C6-C12 aryl-C1-C4-alkoxy, C1-C6-alkylsulfonylamino-C1-C4-alkoxy, (halogenated C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C6-C12-arylsulfonylamino-C1-C4-alkoxy, (C6-C12 aryl-C1-C6-alkyl) sulfonylamino-C1-C4-alkoxy, C3-C12-heterocyclylsulfonylamino-C1-C4-alkoxy, C3-C12-heterocyclyl-C1-C4-alkoxy, C6-C12-aryloxy, C3-C12-heterocyclyloxy, C1-C6-alkylthio, halogenated C1-C6-alkylthio, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-C1-C6-alkylamino, di-(halogenated C1-C6-alkyl)amino, C1-C6-alkylcarbonylamino, (halogenated C1-C6-alkyl)carbonylamino, C6-C12-arylcarbonylamino, C1-C6-alkylsulfonylamino, (halogenated C1-C6-alkyl)sulfonylamino, C6-C12-arylsulfonylamino or optionally substituted C3-C12-heterocyclyl; W is —NR8— or a bond; A1 is optionally substituted C1-C4-alkylene or a bond; Q is —S(O)2— or —C(O)—; Y is —NR9— or a bond; A2 is optionally substituted C1-C4-alkylene, C1-C4-alkylene-CO—, —CO—C1-C4-alkylene, C1-C4-alkylene-O—C1-C4-alkylene, C1-C4-alkylene-NR10—C1-C4-alkylene, optionally substituted C2-C4-alkenylene, optionally substituted C2-C4-alkynylene, optionally substituted C6-C12-arylene, optionally substituted C6-C12-heteroarylene or a bond; X1 is —O—, —NR11—, —S—, optionally substituted C1-C4-alkylene, optionally substituted C2-C4-alkenylene, or optionally substituted C2-C4-alkynylene, wherein -Y-A2-X1- comprises at least 2, 3 or 4 atoms in the main chain; R2 is hydrogen, halogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, —CN, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C2-C6-alkenyloxy, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylcarbonyloxy, C1-C6-alkylthio, C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, aminosulfonyl, amino, C1-C6-alkylamino, C2-C6-alkenylamino, nitro or optionally substituted C3-C12-heterocyclyl, or two radicals R2 together with the ring atoms of A to which they are bound form a 5- or 6 membered ring; R3 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy, or two radicals R3 together with the carbon atom to which they are attached form a carbonyl group; R4 is hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, C6-C12-aryl-C1-C4-alkyl, C3-C12-cycloalkyl, —CHO, C1-C4-alkylcarbonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbonyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxycarbonyl, C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, —C(═NH)NH2, —C(═NH)NHCN, C1-C6-alkylsulfonyl, C6-C12-arylsulfonyl, amino, —NO or C3-C12-heterocyclyl; X2 is >CR12aR12b; X3 is a bond; R5 is optionally substituted C6-C12-aryl, optionally substituted C3-C12-cycloalkyl, or optionally substituted C3-C12-heterocyclyl; R6 is hydrogen or C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; R8 is hydrogen or C1-C6-alkyl; R9 is hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl, amino-C1-C6-alkyl, optionally substituted C6-C12-aryl-C1-C4-alkyl or C3-C12-heterocyclyl; or R9, R1 together are C1-C4-alkylene; or R9 is C1-C4-alkylene that is bound to a carbon atom in A2 and A2 is C1-C4-alkylene or to a carbon atom in X1 and X1 is C1-C4-alkylene; R10 is hydrogen, C1-C6-alkyl or C1-C6-alkylsulfonyl; R11 is hydrogen or C1-C6-alkyl, or R9, R11 together are C1-C4-alkylene, R12a is hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy; R12b is hydrogen or C1-C6-alkyl, or R12a, R12b together are optionally substituted C1-C4-alkylene, wherein one —CH2— of C1-C4-alkylene may be replaced by an oxygen atom or —NR14—; R13a is hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy; R13b is hydrogen or C1-C6-alkyl, or R13a, R13b together are optionally substituted C1-C4-alkylene, wherein one —CH2- of C1-C4-alkylene may be replaced by an oxygen atom or —NR15—; R14 is hydrogen or C1-C6-alkyl; and R15 is hydrogen or C1-C6-alkyl; or a physiologically tolerated salt thereof.
地址 Wiesbaden DE