PIPERIDINE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS

摘要

The present invention discloses compounds of formula (I) any of its enantiomers or any mixture thereof, or a pharmaceutically-acceptable addition salt thereof, wherein X is O, S, or NR3, wherein R3 is hydrogen, alkyl, or aryl which may be substituted one or more times with substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, nitro, cyano, trifluoromethyl, aryl, arylalkyl, aryloxy and arylalkyloxy; m is 0, 1, or 2; n is 0, 1, or 2; R is cycloalkyl, cycloalkylalkyl, (aryl)¿p?-alkyl, (aryl)p-alkenyl, or (aryl)p-alkynyl, wherein the aryl group may be substituted one or more times with substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, nitro, cyano and trifluoromethyl, and p is 0, or 1; one of R?1 and R2¿ is -O-Z, or -S-Z, wherein Z is hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkylalkyl; arylalkyl, arylalkenyl, arylalkynyl, or aryl-CO-, wherein the aryl groups may be substituted one or more times with substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, nitro, cyano and trifluoromethyl; or Z is -(CH¿2?)o-CO-R?2¿, -(CH¿2?)o-COOR?2¿, -(CH¿2?)o-CONR?2R3¿, or -(CH¿2?)o-Het, wherein o is 0, 1, 2, 3, 4, or 5 and R?2 and R3¿ each independently are hydrogen, or alkyl, and Het is a five- or six-membered monocyclic heterocyclic ring; or Z is -(CH¿2)o-WR?4, or (II), wherein o is 0, 1, 2, 3, 4, or 5, W and W' each independently are O, or S, and R?4 and R5¿ each independently are hydrogen, or alkyl, or wherein R?4 and R5¿ together is -(CH¿2?)q-, wherein q is 2, or 3; and the other of R?1 and R2¿ is hydrogen, alkoxy, or alkoxyalkoxy; or R?1 and R2¿ together form a chain -W-(CH¿2?)q-W'-, wherein W and W' each independently are O, or S and q is 2, or 3; Ar is aryl which may be subsittuted one or more times with substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, nitro, cyano, trifluoromethyl, aryl, arylalkyl, aryloxy, and arylalkyloxy. The compounds are useful as pharmaceuticals, for example, in the treatment of ischemia, anoxia, migraine and psychosis.