Patent ID: 6277859
Filing Date: 2001-08-21
Classification: A61P,C07D

Abstract:
A morphinan derivative represented by the formula (I) or its pharmacologically acceptable acid addition salt: ##STR171##wherein,represents a single or double bond;R.sup.1 represents an alkyl group having 1-5 carbon atoms, a cycloalkylalkyl group having 4-7 carbon atoms, a cycloalkenylalkyl group having 5-7 atoms, an aryl group having 6-12 carbon atoms, an aralkyl group having 7-13 carbon atoms, an alkenyl group having 4-7 carbon atoms, an allyl group, a furan-2-ylalkyl group having 1-5 alkyl carbon atoms, or a thiophen-2-ylalkyl group having 1-5 alkyl carbon atom;R.sup.2 represents a hydrogen atom, a hydroxy group, a nitro group, an alkanoyloxy group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon atoms, or --NR.sup.9 R.sup.10 ;R.sup.9 represents a hydrogen atom or an alkyl group having 1-5 carbon atoms;R.sup.10 represents a hydrogen atom, an alkyl group having 1-5 carbon atoms or --C(.dbd.O)R.sup.11 ;R.sup.11 represents a hydrogen atom, a phenyl group or an alkyl group having 1-5 carbon atoms, R.sup.3 represents a hydrogen atom, a hydroxy group, an alkanoyloxy group having 1-5 carbon atoms or an alkoxy group having 1-5 carbon atoms;A represents --NR.sup.4' C(.dbd.Y)--, --NR.sup.4 C(.dbd.Y)Z--, --NR.sup.4' SO.sub.2 --, --NR.sup.4' --, or --OC(OR.sup.4)R.sup.4 -- where Y and Z each independently represent NR.sup.4, S or O, R.sup.4 represents a hydrogen atom, a straight-chain or branched alkyl group having 1-5 carbon atoms or an aryl group having 6-12 carbon atoms, and wherein R.sup.4 may be identical or different, and R.sup.4' represents a hydrogen atom, a straight-chain or branched alkyl group having 1-5 carbon atoms or an aryl group having 6-12 carbon atoms,B represents a valence bond, a straight-chain or branched alkylene group having 1-14 carbon atoms which may be substituted with one or more types of substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, a straight chain or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds and/or triple bonds and having 2-14 carbon atoms which may be substituted with one or more substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, or a straight-chain or branched saturated or unsaturated hydrocarbon containing from 1 to 5 thioether, ether and/or amino bonds having 1-14 carbon atoms wherein no heteroatom is bonded directly to A;R.sup.5 represents a hydrogen atom or an organic group having the structure below which may be substituted with one or more substituent groups selected from the group consisting of an alkyl group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, an isothiocyanate group, a trifluoromethyl group and a methylenedioxy group; ##STR172##wherein Q is N, O or S, T is CH, N, S or O, 1 is 0-5, m, n.gtoreq.0 and m+n.ltoreq.5;R.sup.8 represents a hydrogen atom, an alkyl group having 1-5 carbon atoms or an alkanoyl group having 1-5 carbon atoms;with proviso thata) when A represents --NR.sup.4' C(.dbd.Y)--, --NR.sup.4' C(.dbd.Y) Z--or --NR.sup.4 SO.sub.2 --, and NR.sup.4 represents a straight-chain or branched alkyl group having 1-5 carbon atoms or an aryl group having 6-12 carbon atoms, then R.sup.1 represents an alkyl group having 1-2 carbon atoms, a cycloalkenylalkyl group having 5-7 carbon atoms, an aryl group having 6-12 carbon atoms, an aralkyl group having 7-13 carbon atoms, a furan-2-ylalkyl group having 1-5 carbon atoms or thiophen-2-ylalkyl group having 1-5 carbon atoms;b) when A represents --NHC(.dbd.0)--, and R.sup.5 represents a hydrogen atom, then B represents a straight-chain or branched alkylene having 3-14 carbon atoms (which may be substituted with one or more types of substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, trifluoromethyl group and a phenoxy group), a straight-chain or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds and/or triple bonds and having 3-14 carbon atoms, which may be substituted with one or more substituents selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, trifluoromethyl group and a phenoxy group, or a straight-chain or branched saturated or unsaturated hydrocarbon containing from 1 to 5 thioether, ether and/or amino bonds having 1-14 carbon atoms wherein no heteratom is bonded directly to A;c) when A represents --NHC(.dbd.O)--, B presents a valence bond, and R.sup.5 represents a phenyl group, then R.sup.5 must be substituted with at least one substitutent selected from the group consisting of an alkyl group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, an isothiocyanate group, a trifluoromethyl group and a methylenedioxy group;d) when A represents --NH--, and R.sup.5 represent a hydrogen atom, then B represents a straight-chain or branched alkylene group having 3-14 carbon atoms, which may be substituted with one or more types of substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, a straight-chain or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds and/or triple bonds and having 2-14 carbon atoms, which may be substituted with one or more substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, or a straight-chain or branched saturated or unsaturated hydrocarbon containing from 1 to 5 thieoether, ether and/or amino bonds having 1-14 carbon atoms wherein no heteroatom is bonded directly to A;e) when A represents --NH--, B represents a straight-chain alkylene having one carbon atom, and R.sup.5 represents a phenyl group, then R.sup.5 must be substituted with one or more substituents selected from the group consisting of an alkyl group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, an isothiocyatate group, a trifluoromethyl group and a methylenedioxy group; andf) when A represents --NR.sup.4' --, R.sup.4' represents a straight-chain alkyl group having 1 or 2 carbon atoms, and R.sup.5 represents a hydrogen atom, when B represents a straight-chain or branched alkylene group having 3-14 carbon atoms, which may be substituted with one or more substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, a straight-chain or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds and/or triple bonds and having 2-14 carbon atoms, which may be substituted with one or more substituent groups selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, or a straight-chain or branched saturated or unsaturated hydrocarbon containing from 1 to 5 thioether, ether and/or amino bonds having 1-14 carbon atoms wherein no heteroatom is bonded to A;and formula (I) includes the (+) form, (-) form and (.+-.)form.