Patent IL-124641-A (IL)
Title: 1-(1,2-disubstituted piperidinyl)-4-(fused imidazole)-piperidine derivatives pharmaceutical compositions comprising them and their preparation
IPC: A61K31/395
Filed: 1996-12-20
Abstract: Tachykinin antagonistic compounds of the formula 3005 י' בכסלו התשס" ב - November 25, 2001 N-oxide forms, pharmaceutically acceptable addition salts or stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; =Q is =O or =NR3; X is a covalent bond or a bivalent radical of formula -O-, -S-, -NR3; R1 is Ar1, Ar1C1-6 alkyl or di(Ar1)C1-6 alkyl, wherein each C1-6 alkyl group is optionally substituted with hydroxy, C1-4 alkyloxy, oxo or a ketalized oxo substituent of formula -O-CH2-CH2-O or -O- CH2-CH2- CH2-O-; R2 is Ar2, Ar2 C1-6 alkyl, Het or HetC1-6 alkyl; R3 is hydrogen or C1-6 alkyl; L is a radical of the formula wherein the dotted line is an optional bond; each -A-B- independently is a bivalent radical of formula wherein each Y independently is a bivalent radical of formula -O-, -S- or NR8-; each R7 independently is C1-6 alkyl; halo; ethenyl substituted with carboxyl or alkyloxycarbonyl; hydroxy C1-6 alkyl; formyl; carboxyl or hydroxycarbonyl C1-6 alkyl; or R7 is hydrogen in case -A-B- is a radical of formula (b-1) or (b-2); R8 is hydrogen, C1-6 alkyl or C1-6 alkylcarbonyl; each Z independently is Z1 or Z2; wherein Z1 is a bivalent radical of formula -CH2-, -CH2-CH2- or -CH=CH-; provided that when L is a radical of formula (a-1) and the dotted line is an extra bond, then Z1 is other than -CH2-; Z2 is a bivalent radical of formula -CH2-CHOH-, -CH2-O-, -CH20C(=O)- or -CH2-C(=NOH)-, provided that the -CH2- 3006 י' בכסלו התשס" ב - November 25, 2001 moiety of said bivalent radicals is connected to the nitrogen of the imidazole ring; each R4 independently is hydrogen; C1-6 alkyl; halo; ethenyl substituted with carboxyl or C1-6 alkyloxycarbonyl; C1-6 alkyl substituted with carboxyl or C1-6 alkyloxycarbonyl; hydroxy alkyl; formyl or carboxyl; each R5 independently is hydrogen, C1-6 alkyl, hydroxy C1-6 alkyl, Ar1 or halo; or R4 and R5 taken together may form a bivalent radical of formula- CH=CH-CH=CH or =CH2-CH2-CH2-CH2; each R6 is hydrogen, C1-6 alkyl or Ar1C1-6 alkyl; Ar1 is phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from halo, C1-4 alkyl, halo C1-4 alkyl, cyano, aminocarbonyl, C1-4 alkyloxy or halo C1-3 alkyloxy; Ar2 is naphthalenyl; phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from hydroxy, halo, cyano, nitro, amino, mono- or di(C1-4 alkyl) amino, C1-4 alkyl, halo C1-4 alkyl, C1-4 alkyloxy, halo C1-4 alkyloxy, carboxyl, C1-4 alkyloxycarbonyl, aminocarbonyl and mono- or di(C1-4 alkyl)- aminocarbonyl; and Het is a monocyclic heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl; or a bicyclic heterocycle selected from quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl and benzothienyl; each monocyclic and bicyclic heterocycle may optionally be substituted on a carbon atom by 1 or 2 substituents selected from halo, C1-4 alkyl or mono- di- or tri(halo) methyl.