发明名称 AMINOINDANE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY
摘要 The present invention relates to aminoindane derivatives of the formula (I);;or a physiologically tolerated salt thereof.;The invention relates to pharmaceutical compositions comprising such aminoindane derivatives, and the use of such aminoindane derivatives for therapeutic purposes. The aminoindane derivatives are GlyT1 inhibitors.
申请公布号 US2014309206(A1) 申请公布日期 2014.10.16
申请号 US201414317104 申请日期 2014.06.27
申请人 ABBOTT LABORATORIES ;ABBVIE DEUTSCHLAND GMBH & CO KG 发明人 Pohlki Frauke;Lange Udo;Amberg Wilhelm;Ochse Michael;Behl Berthold;Hutchins Charles W.
分类号 C07C311/14;C07D231/18;C07D205/04;C07D403/12;C07C311/10;C07D233/84 主分类号 C07C311/14
代理机构 代理人
主权项 1. Aminoindane derivatives of the formula (I) wherein A is a 5- or 6-membered ring; 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, 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, optionally substituted C2-C4-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 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; 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-arylC1-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; R4b is hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, 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 R4a, R4b together are optionally substituted C1-C6-alkylene, wherein one —CH2— of C1-C4-alkylene may be replaced by an oxygen atom or —NR16; 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; 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 carbonyl or 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 carbonyl or 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; R15 is hydrogen or C1-C6-alkyl; and R16 is hydrogen or C1-C6-alkyl, or a physiologically tolerated salt thereof.
地址 Abbott Park IL US