发明名称 Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy
摘要 The present invention relates to phenalkylamine derivatives of the formula (I); or a physiologically tolerated salt thereof. ;The invention relates to pharmaceutical compositions comprising such phenalkylamine derivatives, and the use of such phenalkylamine derivatives for therapeutic purposes. The phenalkylamine derivatives are GlyT1 inhibitors.
申请公布号 US9238619(B2) 申请公布日期 2016.01.19
申请号 US201414282712 申请日期 2014.05.20
申请人 AbbVie Deutschland GmbH & Co. KG;AbbVie Inc. 发明人 Pohlki Frauke;Lange Udo;Amberg Wilhelm;Ochse Michael;Behl Berthold;Hornberger Wilfried;Mezler Mario;Hutchins Charles W.;Turner Sean
分类号 A61K31/135;C07C211/25;C07C311/06;C07C311/04;C07C311/05;C07C311/10;C07D205/04;C07D207/08;C07D207/267;C07D231/18;C07D233/42;C07D295/135;C07D401/12;C07D403/12;C07D233/84 主分类号 A61K31/135
代理机构 Michael Best & Friedrich LLP 代理人 Mueller Lisa V.;Michael Best & Friedrich LLP
主权项 1. A method for treating a neurologic disorder selected from the group consisting of dementia, cognitive impairment, and attention deficit disorder, a psychiatric disorder selected from the group consisting of anxiety disorder, depression, bipolar disorder, schizophrenia, and psychosis, or pain in a mammalian patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of formula (I) wherein R is R1—W-A1-Q-Y-A2-X1—; 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, C1-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-C41-alkynylene; 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 to which they are bound form a 5- or 6 membered ring; R3 is hydrogen or C1-C6-alkyl; X2 is —O—, —NR6—, —S—, >CR12aR12b or a bond; X3 is —O—, —NR7—, —S—, >CR13aR13b or a bond; R5 is optionally substituted C6-C12-aryl, optionally substituted C3-C12-cycloalkyl or optionally substituted C3-C12-heterocyclyl; Y1 is >CR14aR14b or a bond; Y2 is >CR15aR15b or a bond; R4a 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; or R4a, R3 together are optionally substituted C1-C6-alkylene; or R4a, R14a together are optionally substituted C1-C6-alkylene; R4b is hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C3-C12-cycloalkyl CH2CN, —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; or R4aR4b together are optionally substituted C1-C6-alkylene, wherein one —CH2— of C1-C6-alkylene may be replaced by an oxygen atom or —NR16; or 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, C1-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy; R12b is hydrogen or C1-C6-alkyl, or R12a, R12b together are carbonyl or optionally substituted C1-C4-alkylene, wherein one —CH2— of C1-C4-alkylene may be replaced by an oxygen atom or —NR17—; 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 carbonyl or optionally substituted C1-C4-alkylene, wherein one —CH2— of C1-C4-alkylene may be replaced by an oxygen atom or —NR18—; R14a is hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy; R14b is hydrogen or C1-C6-alkyl, or R14a, R14b together are carbonyl or optionally substituted C1-C4-alkylene, wherein one or two —CH2— of C1-C4-alkylene may be replaced by an oxygen atom or —NR19—; R15a is hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy; R15b is hydrogen or C1-C12-alkyl, or R15a, R15b together are carbonyl or optionally substituted C1-C4-alkylene, wherein one or two —CH3— of C1-C4-alkylene may be replaced by an oxygen atom or —NR19—; R16 is hydrogen or C1-C6-alkyl; R17 is hydrogen or C1-C6-alkyl; R18 is hydrogen or C1-C6-alkyl, and R19 is hydrogen or C1-C6-alkyl, or a physiologically tolerated salt thereof.
地址 Wiesbaden DE