Patent IL-124640-A (IL)
Title: 1-(1, 2-disubstituted piperidinyl) -4-substituted piperidine derivatives, a process for their preparation and pharmaceutical compositions comprising them
IPC: A61K31/4465
Filed: 1996-12-20
Abstract: Tachykinin antagonist compounds of the formula 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; p is 0, 1 or 2; =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 subsituted with hydroxy, C1-4 alkyloxy, oxo or a ketalized oxo substituent of formula -O-CH2-CH2- or -O-CH2-CH2-CH2-O-; R2 is Ar2; Ar2C1-6 alkyl; Het or Het C1-6 alkyl; R3 is hydrogen or C1-6 alkyl; R4 is hydrogen; C1-4 alkyloxy C1-4 alkyl; hydroxy C1-4 alkyl; carboxyl; C1-4 alkyloxycarbonyl or Ar3; R5 is hydrogen; hydroxy; Ar3; Ar3 C1-6 alkyloxy; di(Ar3) C1-6 alkyloxy; Ar3 C1-6 alkylthio; di (Ar3) C1-6 alkylthio; Ar3 C1-6 alkylsulfoxy; di(Ar3)C1-6 alkylsulfoxy; Ar3C1-6 alkylsufonyl; di(Ar3) C1-6 alkylsufonyl; -NR7R8; C1-6 alkyl substituted with -NR7R8; or a radical of formula 1104 י" ב בסיון התשס" ב - May 23, 2002 wherein R7 is hydrogen; C1-6 alkyl; pyridinyl or Ar3; R8 is hydrogen; C1-6 alkyl; Ar3 C1-6 alkyl; di(Ar3) C1-6 alkyl; imidazolyl substituted with Ar3, C1-6 alkyl or Ar3 C1-6 alkyl; benzoxazolyl or benzothiazolyl; R9 is hydrogen; hydroxy; C1-6 alkyl; C1-6 alkyloxy; Ar3; Ar3 C1-6 alkyl; di (Ar3) C1-6 alkyl; amino; mono- or di (C1-6 alkyl) amino; imidazolyl; imidazolyl subsituted with Ar3 C1-6 alkyl or Ar3 C1-6; pyrrolidinyl; piperidinyl; homopiperidinyl; morpholinyl or thiomorpholinyl; R10 is hydrogen or C1-6 alkylcarbonyl; R11 is hydrogen; halo or mono-, di-or tri(halo) methyl; Y is Y1 or Y2, wherein Y1 is a covalent bond; C1-6 alkanediyl; -NR7 or -C1-6 alkanediyl-NR7-; or Y2 is -O-, provided that R9 is other than hydroxy or C1-6 alkyloxy; R4 and R5 may also be taken together to form a bivalent radical of the formula O-CH2-CH2-O- or -C(=O)-NR3- CH2-NR7-; R6 is hydrogen: hydroxy; C1-6 alkyloxy; C1-6 alkyl or Ar3 C1-6 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 C1-4 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, C1-4 alkyloxy, halo C1-4 alkyloxy, carbonyl, C1-4 alkyloxycarbonyl, aminocarbonyl and mono-or di (C1-4 alkyl) aminocarbonyl; Ar3 is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, amino, nitro, aminocarbonyl, C1-6 alkyl, halo C1-6 alkyl or C1-6 alkyloxy; and Het is a monocyclic heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl; or a bicylic heterocycle selected from quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazoyl, benzofuranyl and benzothienyl; each monocyclic and bicylic 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. 1105 י" ב בסיון התשס" ב - May 23, 2002