Claims
- 1. A morphinan derivative of the formula (I): whereinY 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: whereinQ 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.
- 2. The morphinan derivative or the pharmaceutically acceptable acid addition salt thereof according to claim 1, wherein said A is —C(═O)—NR6—, wherein R6 has the same meanings as defined above.
- 3. The morphinan derivative or the pharmaceutically acceptable acid addition salt thereof according to claim 2, wherein said R6 is C1-C5 alkyl, C3-C7 alkenyl, C3-C7 alkynyl, C6-C12 aryl, or C7-C13 aralkyl.
- 4. The morphinan derivative or the pharmaceutically acceptable acid addition salt thereof according to claim 1, wherein said A is —NR6—C(═O)—, wherein R6 has the same meanings as defined above.
- 5. The morphinan derivative or a pharmaceutically acceptable acid addition salt thereof according to claim 1, wherein said R8 is cyclopropylmethyl.
- 6. A pharmaceutical composition comprising as an effective component an effective amount of said morphinan derivative or the pharmaceutically acceptable acid addition salt thereof according to claim 1.
- 7. A method for treating pain comprising administering an effective amount of said morphinan derivative or the pharmaceutically acceptable acid addition salt thereof according to claim 1.
- 8. A method for treating pain comprising administering an effective amount of said morphinan derivative or the pharmaceutically acceptable acid addition salt thereof according to claim 1, which has an opioid ε-receptor agonist activity.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 9-076340 |
Mar 1997 |
JP |
|
Parent Case Info
This application is the national phase under 35 U.S.C. §371 of prior PCT International Application No. PCT/JP98/01376 which has an International filing date of Mar. 27, 1998 which designated the United States of America now WO 98/43978 published Oct. 8, 1998.
PCT Information
| Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
| PCT/JP98/01376 |
|
WO |
00 |
11/25/1998 |
11/25/1998 |
| Publishing Document |
Publishing Date |
Country |
Kind |
| WO98/43978 |
10/8/1998 |
WO |
A |
Foreign Referenced Citations (4)
| Number |
Date |
Country |
| 49-61188 |
Jun 1974 |
JP |
| 61-63658 |
Apr 1986 |
JP |
| 3-163083 |
Jul 1991 |
JP |
| 93-15081 |
Aug 1993 |
WO |
Non-Patent Literature Citations (3)
| Entry |
| Lessor, R.A. et al.: Probes for narcotic receptor mediated phenomenon. J. med. Chem. vol. 29, pp. 2136-2141, 1986. |
| Jacobson, A.E. et al.: Probes for narcotic receptor mediated phenomenon. Life Sci. vol. 33, suppl. 1, pp. 159-162, 1983. |
| Piggot, N.G. et al.: Molecular modeling of fumaramido and cinnamoylamido derivatives in epoxy-morphinans. Analgesia. vol. 1, pp. 647-650, 1995. |
Patent Grant
6187782
