Patent ID: 6187782
Filing Date: 2001-02-13
Classification: C07D

Abstract:
A morphinan derivative of the formula (I): ##STR80##whereinY is single bond or double bond;R.sup.1 is hydrogen, hydroxy, C.sub.1 -C.sub.5 alkoxy, C.sub.1 -C.sub.5 alkanoyloxy or C.sub.7 -C.sub.13 aralkyloxy;R.sup.2 is hydrogen or C.sub.1 -C.sub.5 alkyl;R.sup.3 and R.sup.4 independently are hydrogen, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.5 alkyl or phenyl;A is --X(.dbd.O)--NR.sup.6 -- or --NR.sup.6 --X(.dbd.O)--, wherein X is carbon or S.dbd.O, R.sup.6 is hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.7 alkenyl, C.sub.3 -C.sub.7 alkynyl, C.sub.6 -C.sub.12 aryl or C.sub.7 -C.sub.13 aralkyl;B is(1) valence bond,(2) C.sub.1 -C.sub.14 straight or branched alkylene, wherein said C.sub.1 -C.sub.14 straight or branched alkylene may be substituted with at least one substituent selected from the group consisting of C.sub.1 -C.sub.5 alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, trifluoromethyl, phenyl and phenoxy, and that 1 to 3 methylene groups therein may be substituted by carbonyl group,(3) C.sub.2 -C.sub.14 linear or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds and/or triple bonds, wherein said C.sub.2 -C.sub.14 linear or branched acyclic unsaturated hydrocarbon may be substituted with at least one substituent selected from the group consisting of C.sub.1 -C.sub.5 alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, trifluoromethyl, phenyl and phenoxy, and that 1 to 3 methylene groups therein may be substituted by carbonyl group, or(4) C.sub.1 -C.sub.14 straight or branched saturated or unsaturated hydrocarbon containing 1 to 5 thioether bonds, ether bonds and/or amino bonds, wherein 1 to 3 methylene groups in said C.sub.1 -C.sub.14 straight or branched saturated or unsaturated hydrocarbon may be substituted by carbonyl group;R.sup.5 is hydrogen, cyano, or an organic group having the following skeleton: ##STR81##whereinQ is --NH--, --S-- or --O--,T is --CH.sub.2 --, --NH--, --S-- or --O--,d is a number from 0 to 5, ande and f independently are numbers of not less than 0 whereas the total of e and f is not more than 5,wherein said organic group may be substituted with at least one substituent selected from the group consisting of C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, hydroxy, C.sub.1 -C.sub.5 alkoxycarbonyl, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, phenyl, phenoxy and methylenedioxy,wherein(1) when A is --X(.dbd.O)--NR.sup.6, --B--R.sup.5, R.sup.6 and nitrogen to which --B--R.sup.5 and R.sup.6 are bound may cooperatively form a heterocyclic ring selected from the group consisting of morpholine, piperidine, pyrrolidine, piperazine, N-methylpiperazine, N-phenylpiperazine, indoline, tetrahydroquinoline and tetrahydroisoquinoline, or(2) when A is --NR.sup.6 --X(.dbd.O)--, --B--R.sup.5 and R.sup.6 may cooperatively form C.sub.2 -C.sub.6 alkylene or ##STR82##wherein a and b independently are numbers of not less than 0, the total of a and b being not more than 4; andR.sup.8 is C.sub.4 -C.sub.7 cycloalkylalkyl or C.sub.7 -C.sub.13 aralkyl;or a pharmaceutically acceptable acid addition salt thereof, provided that when A is --NH--C(.dbd.O)--, B is not --CH.dbd.CH-- or R.sup.5 is not hydrogen.