Patent IL-124321-A (IL)
Title: Esters of 3-hydroxypiperidinemethanol derivatives, intermediates and process for their preparation and pharmaceutical compositions containing them
IPC: C07D401/06
Filed: 1997-02-07
Abstract: A compound 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 is C1-6 alkyloxy, C2-6 alkenyloxy or C2-6 alkynyloxy; R2 is hydrogen or C1-6 alkyloxy, or taken together R1 and R2 may form a bivalent radical of formula -O-CH2-O-(a-1), -O-CH2-CH2-(a-2), -O-CH2-CH2-O-(a-3), -O-CH2-CH2-CH2-(a-4), -O-CH2-CH2-CH2-O-(a-5), -O-CH2-CH2CH2CH2-(a-6), wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C1-6 alkyl, R3 is hydrogen or halo; R4 is hydrogen or C1-6 alkyl; L is C3-6 cycloalkyl, C5-6 cycloalkanone, C2-6 alkenyl optionally substituted with aryl, or L is a radical of formula -Alk-R5(b-1), -Alk-X-R6(b-2), -Alk-Y-C(=O)-R8(b-3), or -Alk-Y-C(=O)-NR10R11(b-4), wherein each Alk is C1-12alkanediyl; and R5 is hydrogen, cyano, C1-6 alkylsulfonylamino, C3-6 cycloalkyl, C5-6 cycloalkanone, aryl, di(aryl)methyl or Het1; R6 is hydrogen, C1-6 alkyl, hydroxy C1-6 alkyl, C3-6 cycloalkyl, aryl or Het2; X is O, S, SO2 or NR7; said R7 being hydrogen, C1-6 alkyl or aryl; R8 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, aryl, aryl C1-6 alkyl, di(aryl)methyl, C1-6 alkyloxy or hydroxy; Y is NR9 or a direct bond; said R9 being hydrogen, C1-6 alkyl or aryl; 3073 י' בטבת התשס" ד - January 4, 2004 R10 and R11 each independently are hydrogen, C1-6 alkyl, C3-6 cycloalkyl, aryl or aryl C1-6 alkyl, or R10 and R11 combined with the nitrogen atom bearing R10 and R11 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 R10 and R11 combined with the nitrogen bearing R10 and R11 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C1-6 alkyl; each aryl being unsubstituted phenyl or phenyl substituted with 1, 2 or 3 substituents each independently selected from halo, hydoxy, C1-6 alkyl, C1-6 alkyloxy, amino-sulfonyl, C1-6 alkylcarbonyl, nitro, trifluoromethyl, amino or aminocarbonyl; and Het1 and Het2 each independently are selected from furan; furan substituted 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 alkyl; pyrolidinyl; 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 substitutents 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- or di(C1-6 alkyl)amino and C1-6 alkyloxycarbonyl; Het1 can also be a radical of formula Het1 and Het2 each independently can also be selected from the radicals of formula R12 and R13 each independently are hydrogen or C1-4 alkyl. Also claimed are intermediate compounds wherein L is hydrogen. 3074 י' בטבת התשס" ד - January 4, 2004