GASTROKINETIC BICYCLIC BENZAMIDES OF 3- OR 4-SUBSTITUTED 4-(AMINOMETHYL)-PIPERIDINE DERIVATIVES, INTERMEDIATES THEREOF, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM

摘要

Compounds of the formula a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid or base addition salt thereof, wherein R1 and R2 taken together form a bivalent radical of the formula -O-CH2-O-, -O-CH2-CH2-, -O-CH2-CH2-O-, -O-CH2-CH-CH2-, -O-CH2-CH2-CH2-O-, -O-CH2-CH2-CH2-CH2- 1418 א' בתמוז התשס" ד - June 20, 2004 wherein in said bivalent radical one or two hydrogen atoms may be substituted with C1-6 alkyl, R3 is hydrogen or halo; R4 is hydrogen or C1-6 alkyl; R5 is hydrogen or C1-6 alkyl; L is hydrogen, C3-6 cycloalkyl, C5-6 cycloalkanone or C2-6 alkenyl, or L is a radical of the formula -Alk-R6, -Alk-X-R7, -Alk-Y-C(=O)-R9 or -Alk-Y-C(=O)-NR11R12 wherein each Alk is C1-12 alkenediyl; and R6 is hydrogen, hydroxy, cyano, C1-6 alkylsulfonylamino, C3-6 cycloalkyl, C5-6 cycloalkanone, or Het1; R7 is hydrogen, C1-6 alkyl, hydroxy C1-6 alkyl, C3-6 cycloalkyl, or Het2; X is O, S, SO2 or NR8; said R8 being hydrogen or C1-6 alkyl; R9 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkyloxy or hydroxy; Y is NR10 or a direct bond; said R10 being hydrogen or C1-6 alkyl; R11 and R12 each independently are hydrogen, C1-6 alkyl, C3-6 cycloalkyl, or R11 and R12 combined with the nitrogen atom bearing R11 and R12 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C1-6 alkyl, amino or mono or di(C1-6 alkyl) amino, or said R11 and R12 combined with the nitrogen bearing R11 and R12 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C1-6 alkyl; and Het1 and Het2 each independently are selected from furan; furan subsituted with C1-6 alkyl or halo; tetrahydrofuran; a tetrahydrofuran substituted with C1-6 alkyl; a dioxolane; a dioxolane substituted with C1-6 alkyl, a dioxane; a dioxane substituted with C1-6 alkyl; tetrahydropyran; a tetrahydropyran substituted with C1-6; pyrrolidinyl; pyrrolidinyl substituted with one or two substituents each independently selected from halo, hydroxy, cyano, or C1-6 alkyl; pyridinyl; pyridinyl substituted with one or two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl; pyrimidinyl; pyrimidinyl substituted with one or two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino and mono and di(C1-6 alkyl) amino; pyridazinyl; pyridazinyl substituted with one or two substituents each independently selected from hydroxy, C1-6 alkyloxy, C1-6 alkyl or halo; pyrazinyl; pyrazinyl substituted with one or two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino, mono- and di(C1-6 alkyl) amino and C1-6 alkyloxycarbonyl; Het1 can also be a radical of the formula Het1 and Het2 each independently can also be selected from the radicals of the formula R13 and R14 each independently are hydrogen or C1-4 alkyl. 1419 א' בתמוז התשס" ד - June 20, 2004