Patent ID: 6124279
Filing Date: 2000-09-26
Classification: A61P,C07D

Abstract:
A compound of formula I: ##STR3## wherein m is 2 or 3;D is a residue of formula Ia or formula Ib: ##STR4## wherein Q is phenyl having 0, 1, or 2 substituents independently selected from halo, trifluoromethyl, hydroxy, (C.sub.1 -C.sub.3)alkoxy, (C.sub.1 -C.sub.3)alkyl and methylenedioxy; orQ is thienyl, imidazolyl, benzo[b]thiophenyl or naphthyl, any of which having 0 or 1 halo substituents; orQ is biphenylyl; orQ is carbon-linked indolyl bearing 0 or 1 benzyl substituents at the 1-position;Q.sup.a is hydrogen, (C.sub.1 -C.sub.4)alkyl, or a radical of formula --(CH.sub.2).sub.q --NR.sup.5 R.sup.6 in which q is 2 or 3 and R.sup.5 and R.sup.6 are independently (C.sub.1 -C.sub.4)alkyl or NR.sup.5 R.sup.6 is piperidino or 4-benzylpiperidino;R' and R"" are each independently H or Me, and are attached to carbon atoms;R.sup.1 is hydrogen, methyl or (C.sub.2 -C.sub.6).sub.n -alkyl which may bear a terminal amino radical;R.sup.2 is --C(.dbd.O)R.sup.3, --C(.dbd.O)OR.sup.3 or --C(.dbd.J.sup.1)NHR.sup.3 in which J.sup.1 is oxygen or sulfur and R.sup.3 is hydrogen, (C.sub.1 -C.sub.6)alkyl, phenyl(C.sub.1 -C.sub.3)alkyl (in which the phenyl may bear one or more halo, hydroxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.4)alkyl substituents), pyridyl(C.sub.1 -C.sub.3)alkyl, naphthyl(C.sub.1 -C.sub.3)alkyl, pyridylthio(C.sub.1 -C.sub.3)alkyl, styryl, 1-methylimidazol-2-ylthio(C.sub.1 -C.sub.3)alkyl, aryl (which may bear one or more halo, hydroxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.4)alkyl substituents), heteroaryl (which may bear one or more halo, hydroxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.4)alkyl substituents), or (when R.sup.2 is --COR.sup.3) .alpha.-hydroxybenzyl;J.sup.2 is oxygen or two hydrogens;L.sup.6 is carbonyl or methylene;n is 0, 1, 2 or 3;p is 1 or 2, and when p is 2, n is 1 and J.sup.2 is two hydrogens;r is 0, 1, 2, or 3;R.sup.4 is phenyl, which may bear one or more halo, trifluoromethyl, (C.sub.1 -C.sub.4)alkyl, hydroxy or (C.sub.1 -C.sub.4)alkoxy substituents; naphthyl which may bear one or more halo, trifluoromethyl, (C.sub.1 -C.sub.4)alkyl or hydroxy substituents; pyridyl; thienyl; indolyl; quinolinyl; benzothienyl or imidazolyl; or when L.sup.6 is carbonyl, the group --(CH.sub.2).sub.r --R.sup.4 may additionally represent aryl, heteroaryl or a benzyl group bearing an .alpha.-substituent selected from hydroxy, (C.sub.1 -C.sub.4)alkoxy and (C.sub.1 -C.sub.4)alkyl, and further wherein the aryl, heteroaryl or phenyl portion of the benzyl group may bear one or more substituents selected independently from halo, trifluoromethyl, (C.sub.1 -C.sub.4)alkyl, hydroxy and (C.sub.1 -C.sub.4)alkyl;the values of G, J, M and L are selected from(a) G is a single bond; J is O or S; and M is O, S or NR.sup.12 ;(b) G is a single bond; J is NR.sup.8 ; and M is NR.sup.7 ; and(c) G is a double bond, J is OR.sup.7, SR.sup.7 or NR.sup.9 R.sup.10 ; and M is NR.sup.12 ;whereinR.sup.7 is hydrogen or (C.sub.1 -C.sub.3)alkyl;R.sup.8 is hydrogen, (C.sub.1 -C.sub.3)alkyl, cyano, (C.sub.1 -C.sub.3)alkylsulfonyl or nitro;R.sup.9 and R.sup.10 are independently hydrogen or (C.sub.1 -C.sub.3)alkyl or the radical NR.sup.9 R.sup.10 is pyrrolidino, piperidino, morpholino, thiomorpholino (or its S-oxide) or piperazino (which may bear a (C.sub.1 -C.sub.3)alkyl substituent at the 4-position);R.sup.12 is hydrogen, (C.sub.1 -C.sub.3)alkyl, R.sup.a OC(.dbd.O)CH.sub.2 -- or R.sup.b R.sup.c NC(.dbd.O)CH.sub.2 --;R.sup.a is hydrogen or (C.sub.1 -C.sub.3)alkyl;R.sup.b and R.sup.c are independently hydrogen, (C.sub.1 -C.sub.3)alkyl, phenyl or benzyl;or the N-oxide of said compound of formula I at the piperidino nitrogen indicated by .DELTA.;or a pharmaceutically-acceptable salt of said compound of formula I or said N-oxide;or a quaternary ammonium salt of said compound of formula I in which the piperidino nitrogen indicated by .DELTA. is a quadricovalent ammonium nitrogen wherein the fourth radical on the nitrogen is (C.sub.1 -C.sub.4)alkyl or benzyl and the associated counterion is a pharmaceutically-acceptable anion.