Aminotetraline derivatives, pharmaceutical compositions containing them, and their use in therapy

摘要

The present invention relates to aminotetraline derivatives of the formula (I);
or a physiologically tolerated salt thereof.
;The invention relates to pharmaceutical compositions comprising such aminotetraline derivatives, and the use of such aminotetraline derivatives for therapeutic purposes. The aminotetraline derivatives are GlyT1 inhibitors.

主权项

1. An aminotetraline derivative of the formula (I) wherein A is a 5- or 6-membered ring; 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, —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; n is 0, 1 or 2; R6 is hydrogen or C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; 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.