Remedies for drug addiction

A method for treating cocaine dependence which comprises administering an opioid k receptor agonist, or a pharmacologically acceptable acid-addition salt thereof, to a patient who is dependent on cocaine, wherein said opioid k receptor agonist is represented by the following formula (I):

• wherein
• is a double bond, or a single bond;
• R1is an alkyl group having from 1 to 5 carbon atoms, a cycloalkylalkyl group having from 4 to 7 carbon atoms, a cycloalkenylalkyl group having from 5 to 7 carbon atoms, an aryl group having from 6 to 12 carbon atoms, an aralkyl group having from 7 to 13 carbon atoms, an alkenyl group having from 4 to 7 carbon atoms, an allyl group, a furan-2-ylalkyl group having from 1 to 5 carbon atoms, or a thiophen-2-ylalkyl group having from 1 to 5 carbon atoms;
• R2 is a hydrogen atom, a hydroxy group, a nitro group, an alkanoyloxy group having from 1 to 5 carbon atoms, an alkoxy group having from 1 to 5 carbon atoms, or —NR9R10;
• R9 is a hydrogen atom or an alkyl group having from 1 to 5 carbon atoms;
• R10 is a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms;
• R3 is a hydrogen atom, a hydroxy group, an alkanoyloxy group having from 1 to 5 carbon atoms, or an alkoxy group having from 1 to 5 carbon atoms;
• A is —XC(═Y)—, —XC(═Y)Z—, —X—, or —XSO2, wherein X, Y and Z are, independently of one another, NR4S, or O;
• and R4 is a hydrogen atom, a straight-chain or branched-chain alkyl group having from 1 to 5 carbon atoms;
• and R4 is optionally identical or different in the formula;
• B is a valence bond, a straight-chain or branched-chain alkylene group having from 1 to 14 carbon atoms, wherein the alkylene group is optionally substituted by one or more substituents selected from the group consisting of an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, a trifluoromethyl group, a trifluoromethoxy group, ad a phenoxy group, and wherein one to three methylene groups of the alkylene group is optionally replaced with carbonyl groups, straight-chain or branched-chain acyclic unsaturated hydrocarbon containing from one to three double bonds and/or triple bonds and having from 2 to 14 carbon atoms, wherein the acyclic unsaturated hydrocarbon is optionally substituted by one or more substituents selected from the group consisting of an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, a trifluoromethyl group, a trifluoromethoxy group, and a phenoxy group, and wherein one to three methylene groups of the acyclic unsaturated hydrocarbon is optionally replaced with carbonyl groups, or a straight-chain or branched-chain saturated or unsaturated hydrocarbon containing from one to five thioether, ether, and/or amino bonds and having from 1 to 14 carbon atoms, wherein no hetero atoms are bonded directly to A, and one to three methylene groups of the hydrocarbon is optionally replaced with carbonyl groups;
• and R5 is a hydrogen atom or an organic group having a basic skeleton selected from the group consisting of the following formulas:
• wherein the organic group optionally has at least one substituent selected from the group consisting of an alkyl group having from 1 to 5 carbon atoms, an alkoxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, an isothiocyanate group, a trifluoromethyl group, a trifluoromethoxy group, and a methylenedioxy group;
• R6 is a hydrogen atom;
• R7 is a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms, or an alkanoyloxy group having from 1 to 5 carbon atoms, or R6 and R7 are —O—, —CH2—, —S— together;
• R8 is a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms or an alkanoyl group having from 1 to 5 carbon atoms.

A method of treating opioid μ receptor agonist dependence which comprises administering an opioid k receptor agonist or a pharmacologically acceptable acid-addition salt thereof, wherein said derivative is represented by the following formula (I):

• wherein
• is a double bond, or a single bond;
• R1 is an alkyl group having from 1 to 5 carbon atoms, a cycloalkylalkyl group having from 4 to 7 carbon atoms, a cycloalkenylalkyl group having from 5 to 7 carbon atoms, an aryl group having from 6 to 12 carbon atoms, an aralkyl group having from 7 to 13 carbon atoms, an alkenyl group having from 4 to 7 carbon atoms, an allyl group, a furan-2-ylalkyl group having from 1 to 5 carbon atoms, or a thiophen-2-ylalkyl group having from 1 to 5 carbon atoms;
• R2 is a hydrogen atom, a hydroxy group, a nitro group, an alkanoyloxy group having from 1 to 5 carbon atoms, an alkoxy group having from 1 to 5 carbon atoms, an alkyl group having from 1 to 5 carbon atoms, or —NR9R10;
• R9 is a hydrogen atom or an alkyl group having from 1 to 5 carbon atoms;
• R10 is a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms;
• R10 is a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms, or —C(═O)R11 is a hydrogen atom, a hydroxy group, an alkanoyloxy group having from 1 to 5 carbon atoms;
• A is —XC(═Y)—, —XC(═Y)Z—, —X—, or —XSO2, wherein X, Y and Z are, independently of one another, NR4, S, or O;
• and R4 is a hydrogen atom, a straight-chain or branched-chain alkyl group having from 1 to 5 carbon atoms, or an aryl group having from 6 to 12 carbon atoms;
• and R4 is optionally identical or different in the formula;
• B is a valence bond, a straight-chain or branched-chain alkylene group having from 1 to 14 carbon atoms, wherein the alkylene group is optionally substituted by one or more substituents selected from the group consisting of an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, a trifluoromethyl group, a trifluoromethoxy group, and a phenoxy group, and wherein one to three methylene groups of the alkylene group is optionally replaced with carbonyl groups, a straight-chain or branched-chain acyclic unsaturated hydrocarbon containing from one to three double bonds and/or triple bonds and having from 2 to 14 carbon atoms, wherein the acyclic unsaturated hydrocarbon is optionally substituted by one or more substituents selected from the group consisting of an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, a trifluoromethyl group, a trifluoromethoxy group, and a phenoxy group and wherein one to three methylene groups of the acyclic unsaturated hydrocarbon is optionally replaced with carbonyl groups, or a straight-chain or branched-chain saturated or unsaturated hydrocarbon containing from one to five thioether, ether, and/or amino bonds and having from 1 to 14 carbon atoms, wherein no hetero atoms are bonded directly to A, and one to three methylene groups of the hydrocarbon is optionally replaced with carbonyl groups;
• and R5 is a hydrogen atom or an organic group having a basic skeleton selected from the group consisting of the following formulas:
• wherein the organic group optionally has at least one substituent selected from the group consisting of an alkyl group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, an isothiocyanate group, a trifluoromethyl group, a trifluoromethoxy group, and a methylenedioxy group;
• R6is a hydrogen atom;
• R7is a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms, or an alkanoyloxy group having from 1 to 5 carbon atoms, or R6 and R7 are —O—, —CH2—, —S— together;
• R8 is a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms or an alkanoyl group having from 1 to 5 carbon atoms.

A method of inhibiting dopamine release which comprises administering an opioid K agonistic morphinan derivative or a pharmacologically acceptable acid-addition salt thereof, wherein said derivative is represented by the following formula (I):

• wherein
• is a double bond, or a single bond;
• R1 is an alkyl group having from 1 to 5 carbon atoms, a cycloalkylalkyl group having from 4 to 7 carbon atoms, a cycloalkenylalkyl group having from 5 to 7 carbon atoms, an aryl group having from 6 to 12 carbon atoms, an aralkyl group having from 7 to 13 carbon atoms, an alkenyl group having from 4 to 7 carbon atoms, an allyl group, a furan-2-ylalkyl group having from 1 to 5 carbon atoms, or a thiophen-2-ylalkyl group having from 1 to 5 carbon atoms;
• R2 is a hydrogen atoms, a hydroxy group, a nitro group, an alkanoyloxy group having from 1 to 5 carbon atoms, an alkoxy group having from 1 to 5 carbon atoms, an alkyl group having from 1 to 5 carbon atoms, or —NR9R10;
• R9 is a hydrogen atom or an alkyl group having from 1 to 5 carbon atoms;
• R10 is a hydrogen atom, an alkyl group having from 1 to 5 carbon Atoms, or —C(═O)R11;
• R11 is a hydrogen atom, a phenyl group, or an alkyl group having from 1 to 5 carbon atoms;
• R3 is a hydrogen atom, a hydroxy group, an alkanoyloxy group having from 1 to 5 carbon atoms, or an alkoxy group having from 1 to 5 carbon atoms;
• A is —XC(═Y)Z—, —X—, or —XSO2—, wherein X, Y and Z are, independently of one another, NR4, S, or O;
• and R4 is a hydrogen atom, a straight-chain or branched-chain alkyl group having from 1 to 5 carbon atoms, or an aryl group having from 6 to 12 carbon atoms;
• and R4 is optionally identical or different in the formula;
• B is a valence bond, a straight-chain or branched-chain alkylene group having from 1 to 14 carbon atoms, wherein the alkylene group is optionally substituted by one or more substituents selected from the group consisting of an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, a trifluoromethyl group, a trifluoromethoxy group, and a phenoxy group, and wherein one to three methylene groups of the alkylene group is optionally replaced with carbonyl groups, a straight-chain or branched-chain acyclic unsaturated hydrocarbon containing from one to three double bonds and/or triple bonds and having from 2 to 14 carbon atoms, wherein the acyclic unsaturated hydrocarbon is optionally substituted by one or more substituents selected from the group consisting of an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, a trifluoromethyl group, a trifluoromethoxy group, and a phenoxy group, and wherein one to three methylene groups of the acyclic unsaturated hydrocarbon is optionally replaced with carbonyl groups, or straight-chain or branched-chain saturated or unsaturated hydrocarbon containing from one to five thioether, ether, and/or amino bonds and having from 1 to 14 carbon atoms, wherein no hetero atoms are bonded directly to A, and one to three methylene groups of the hydrocarbon is optionally replaced with carbonyl groups;
• and R5 is a hydrogen atom or an organic group having a basic skeleton selected from the group consisting of the following formulas:
• wherein the organic group optionally has at least one substituent selected from the group consisting of an alkyl group having from 1 to 5 carbon atoms, an alkoxy group having from 1 to 5 carbon atoms, an alkanoyloxy group having from 1 to 5 carbon atoms, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an amino group, a nitro group, a cyano group, an isothiocyanate group, a trifluoromethyl group, a trifluoromethoxy group, and a methylenedioxy group;
• R6 is a hydrogen atom;
• R7 is a hydrogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms, or an alkanoyloxy group having from 1 to 5 carbon atoms, or R6 and R7 are —O—, —CH2—, —S— together;
• R8 is a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms, or an alkanoyl group having from 1 to 5 carbon atoms.