Morphinane derivatives and medicinal use thereof

A morphinan derivative of the formula (I):

• wherein
• Y is single bond or double bond;
• R1 is hydrogen, hydroxy, C1-C5 alkoxy, C1-C5 alkanoyloxy or C7-C13 aralkyloxy;
• R2 is hydrogen or C1-C5 alkyl;
• R3 and R4 independently are hydrogen, fluorine, chlorine, bromine, iodine, C1-C5 alkyl or phenyl;
• A is —X(═O)—NR6— or —NR6—X(═O)—, wherein X is carbon or S═O, R6 is hydrogen, C1-C5 alkyl, C3-C7 alkenyl, C3-C7 alkynyl, C6-C12 aryl or C7-C13 aralkyl;
• B is
• (1) valence bond,
• (2) C1-C14 straight or branched alkylene, wherein said C1-C14 straight or branched alkylene may be substituted with at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 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) C2-C14 linear or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds and/or triple bonds, wherein said C2-C14 linear or branched acyclic unsaturated hydrocarbon may be substituted with at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 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) C1-C14 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 C1-C14 straight or branched saturated or unsaturated hydrocarbon may be substituted by carbonyl group;
• R5 is hydrogen, cyano, or an organic group having the following skeleton:
• wherein
• Q is —NH—, —S— or —O—,
• T is —CH2—, —NH—, —S— or —O—,
• d is a number from 0 to 5, and
• e 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 C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, C1-C5 alkoxycarbonyl, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, phenyl, phenoxy and methylenedioxy,
• wherein
• (1) when A is —X(═O)—NR6, —B—R5, R6 and nitrogen to which —B—R5 and R6 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 —NR6—X(═O)—, —B—R5 and R6 may cooperatively form C2-C6 alkylene or
• wherein a and b independently are numbers of not less than 0, the total of a and b being not more than 4;
• and
• R8 is C4-C7 cycloalkylalkyl or C7-C13 aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof, provided that when A is —NH—C(═O)—, B is not —CH═CH— or R5 is not hydrogen.