Patent IL-124309-A (IL)
Title: Azetidinylalkyl derivatives of n-containing heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them for antagonizing tachykinin
IPC: C07D401/06
Filed: 1996-12-09
Abstract: Compounds of the formula or pharmaceutically acceptable salts thereof, wherein R is C3-C7 cycloalkyl, aryl or C1-C6 alkyl, said C1-C6 alkyl being optionally substituted by fluoro, -COOH, -COO (C1-C4) alkyl, C3-C7 cycloalkyl, adamantyl, aryl or het1, and said C3-C7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C1-C4 alkyl, C3-C7 cycloalkyl, C1-C4 alkoxy, hydroxy, fluoro, fluoro (C1-C4) alkyl and fluoro (C1-C4) alkoxy; 3168 ה' בכסלו התשס" ג - November 10, 2002 A is CO or SO2; R1 is phenyl, benzyl, naphthyl, thienyl, benzothienyl or indolyl, each optionally substituted by 1 or 2 substituents each independently selected from C1-C4 alkyl, C1-C4 alkoxy, halo and trifluoromethyl; R2 is -CO2H, -CONR3R4, -CONR5 (C3-C7 cycloalkyl), -NR5 (C2-C5 alkanoyl), -NR3R4, -NR5CONR5R6, (C3-C7 cycloalkyl-C1-C4 alkyl) R5N-, (C3-C7 cycloalkyl-C1-C4 alkyl)2N-, NR5COCF3, -NR5SO2CF3, -NR5(SO2C1-C4 alkyl), -NR5SO2NR5R6, -NR5(SO2 aryl), -N(aryl) (SO2C1-C4 alkyl), -OR5, -O(C3-C7 cycloalkyl), -SO2NR5R6, het3 or a group of the formula: R3 and R4 are each independently selected from H and C1-C4 alkyl optionally subsituted by hydroxy, C1-C4 alkoxy, -S(O)p(C1-C4 alkyl), amino, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2 or het2; R5 and R6 are each independently selected from H, C1-C4 alkyl and C3-C7 cycloalkyl-C1-C4 alkyl, said C1-C4 alkyl and C3-C7 cycloalkyl-C1-C4 alkyl being optionally substituted by fluoro; R7 is H, C1-C4 alkyl, hydroxyl, fluoro (C1-C4) alkyl or phenyl, said phenyl being optionally substituted by 1 or 2 substituents each independently selected from C1-C4 alkyl, fluoro (C1-C4) alkyl, halo, C1-C4 alkoxy and fluoro (C1-C4) alkoxy; R8 is H, fluoro, hydroxy, C1-C4 alkoxy, C2-C5 alkanoyl or C2-C5 alkanoyloxy; R9 is -NR5R6, -NR5COR5, -NR5SO2CF3, -NR5 (SO2C1-C4 alkyl), -NR5SO2NR5R6, -NR5COO (C1-C4 alkyl), -NR5CONR5R6, -NR5 (SO2 morpholino), -NR5 (SO2 aryl), -N(aryl) (SO2C1-C4 alkyl) or a group of the formula: 3169 ה' בכסלו התשס" ג - November 10, 2002 X is C1-C4 alkylene; X1 is a direct link or C1-C6 alkylene; X2 is a direct link, CO, SO2 or NR5CO; W is methylene, CO, CH(OH), C(OH)2), CH(C1-C4 alkoxy), CHCO2H, CHCO2 (C1-C4 alkyl), CHONR5R6, CHF, CF2, CH (azetidin-1-yl), CH (pyrrolidin-1-yl), CH (piperidin-1-yl), CH(morpholino), CH (benzoxazol-2-yl), CHR9, O, S(O)p, NR5, N(C3-C7 cycloalkyl), NSO2 (C1-C4 alkyl), NSO2NR5R6, NSO2CF3, NSO2 (morpholino), NSO2(aryl), NCONR5R6, NCOR5, NCO(aryl) or NCO2(C1-C4 alkyl); W1 is methylene, CO, CH(OH), C(OH)2, CH(C1-C4 alkoxy), CHCO2H, CHCO2(C1-C4 alkyl), CHCONR5R6, CHF, CF2, CH(azetidin-1-yl), CH (pyrrolidin- 1-yl), CH(piperidin-1-yl), CH(morpholino) or CHR9; W2 is W1, -CH2W1-; -CH2WCH2- or -CH2CH2WCH2-; m is 0, 1 or 2; n is 1 or 2 when W is other than methylene and is 0, 1 or 2 when W is methylene; p is 0, 1 or 2; q is 1 or 2; r is 1, 2, 3, or 4; " aryl" , used in the definition of R, R2, R9 and W, means naphthyl or phenyl, each optionally substituted by C1-C4 alkyl, halo, -OR5, fluoro (C1-C4) alkyl, C2-C5 alkanoyl, -CONR5R6, -SO2NR5R6 or phenyl; " het1" , used in the definition of R, means thienyl or a 5- or 6- membered ring heteroaryl group containing either 1 or 2 nitrogen heteroatoms or one nitrogen heteroatom and one oxygen or sulphur heteroatom, each optionally substituted by 1 or 2 substitutents each independently selected from C1-C4 alkyl, C1-C4 alkoxy, halo, fluoro (C1-C4 alkyl) and fluoro (C1-C4 alkoxy); " het2" , used in the definitions of R3 and R4, means a 4- to 7- membered ring, non-aromatic, heterocyclic group containing 1 or 2 heteroatoms each independently selected from nitrogen, oxygen and S(O)p, said group being optionally C-subsituted by 1 or 2 substituents each independently selected from C1-C4 alkyl, C1-C4 alkoxy and fluoro (C1-C4) alkyl, and said ring nitrogen heteroatom optionally bearing a H, C1-C4 alkyl, C2-C5 alkanoyl, -CONR5R6 or -SO2NR5R6 substituent; and " het3"