Claims
- 1. A method for agonizing or antagonizing the ORL1 (opioid receptor-like) receptor of the nociceptin/orphanin FQ ligand ORL1 receptor system, the method comprising administering, to a cell comprising said receptor system, an effective amount of a composition comprising a morphinan compound of formula I: whereinR1 denotes H, a C1-4 alkyl group or a C2-4 alkenyl group; R2 denotes H, a C1-18 alkyl group, a C2-18 alkenyl group, a heterocyclyl group or an aryl group; R3 denotes a C1-18 alkyl group, a C2-18 alkenyl group, a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C1-4 alkylene group, or a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C2-4 alkenylene group; R4 denotes H, a C1-18 alkyl group, a C2-18 alkenyl group, a C3-7 cycloalkyl or aryl group bound via a C1-4 alkylene group, or a C3-7 cycloalkyl or aryl group bound via a C2-4 alkenylene group, and X denotes O or NR5 where R5 denotes H, a C1-18 alkyl group, a C2-18 alkenyl group, a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C1-4 alkylene group, or a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C2-4 alkenylene group, or an enantiomer, diastereomer, or physiologically compatible salt thereof.
- 2. A method according to claim 1, wherein R2 denotes a C1-10 alkyl group.
- 3. A method according to claim 1, wherein R2 denotes a C2-10 alkenyl group.
- 4. A method according to claim 1, wherein R3 denotes a C1-10 alkyl group.
- 5. A method according to claim 1, wherein R3 denotes a C2-10 alkenyl group.
- 6. A method according to claim 1, wherein R4 denotes H a C1-10 alkyl group.
- 7. A method according to claim 1, wherein R4 denotes a C2-10 alkenyl group.
- 8. A method according to claim 1, wherein R5 denotes a C1-10 alkyl group.
- 9. A method according to claim 1, wherein R5 denotes a C2-10 alkenyl group.
- 10. A method for antagonizing the ORL1 receptor of the nociceptin/orphanin FQ ligand ORL1 receptor system according to claim 1, wherein the morphinan compound is:17-allyl-6,7-didehydro-4,5α-epoxy-3,14-dihydroxy-1′-(o-chlorobenzyl)indolo[6,7:2,′3′]-morphinan hydrochloride, 17-allyl-6,7-didehydro-4,5α-epoxy-3-hydroxy-14-(m-chloro-methoxyphenyl)1′-(m-chlorobenzyl)indolo[6,7:2,′3′]-morphinan hydrochloride, or 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3-hydroxy-14-(o-chloromethoxyphenyl)1′-(o-chlorobenzyl)indolo[6,7:2,′3′]-morphinan hydrochloride.
- 11. A method for agonizing the ORL1 receptor of the nociceptin/orphanin FQ ligand ORL1 receptor system according to claim 1, wherein the morphinan compound is:17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3-hydroxy-14-(methoxynaphthalene)1′-(β-methylnaphthalene)indolo-[6,7:2,′3′]-morphinan hydrochloride or 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-14-hydroxy-3-benzyloxy-1′-(p-methoxycarbonylmethylphenyl)-indolo[6,7:2,′3′]-morphinan hydrochloride.
- 12. A method for the treatment of at least one condition selected from the group consisting of neuropathic pain, anxiolysis, depression, diuresis, urinary incontinence, hypotension, hypertension, senile dementia, Alzheimer's disease, general cognitive dysfunctions, tinnitus, impaired hearing, epilepsy, obesity, and cachexia, the method comprising administering an effective amount of a compound of formula I: whereinR1 denotes H, a C1-4 alkyl group or a C2∝alkenyl group; R2 denotes H, a C1-18 alkyl group, a C2-18 alkenyl group, a heterocyclyl group or an aryl group; R3 denotes a C1-18 alkyl group, a C2-18 alkenyl group, a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C1-4 alkylene group, or a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C2-4 alkenylene group; R4 denotes H, a C1-18 alkyl group, a C2-18 alkenyl group, preferably a C2-10 alkenyl group, a C3-7 cycloalkyl or aryl group bound via a C1-4 alkylene group, or a C3-7 cycloalkyl or aryl group bound via a C2-4 alkenylene group, and X denotes O or NR5 where R5 denotes H, a C1-18 alkyl group, a C2-18 alkenyl group, a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C1-4 alkylene group, or a C3-7 cycloalkyl, aryl or heterocyclyl group bound via a C2-4 alkenylene group, or an enantiomer, diastereomer, or physiologically compatible salt thereof.
- 13. A method according to claim 12, wherein the morphinan compound is selected from the group consisting of:17-allyl-6,7-didehydro-4,5α-epoxy-3,14-dihydroxy-1′-(o-chlorobenzyl)indolo[6,7:2,′3′]-morphinan hydrochloride; 17-allyl-6,7-didehydro-4,5α-epoxy-3-hydroxy-14-(m-chloro-methoxyphenyl)1′-(m-chlorobenzyl)indolo-[6,7:2,′3′]-morphinan hydrochloride; 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3-hydroxy-14-(o-chloromethoxyphenyl)1′-(o-chlorobenzyl)-indolo[6,7:2,′3′]-morphinan hydrochloride; 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3-hydroxy-14-(methoxynaphthalene)1′-(β-methyl-naphthalene)indolo-[6,7:2,′3′]-morphinan hydrochloride; and 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-14-hydroxy-3-benzyloxy-1′-(p-methoxycarbonylmethylphenyl)-indolo[6,7:2,′3′]-morphinan hydrochloride.
CROSS REFERENCE TO RELATED APPLICATIONS
The present application is a continuation of international patent application no. PCT/EP00/07585, filed Aug. 4, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. 199 39 044.4, filed Aug. 18, 1999.
Foreign Referenced Citations (2)
Number |
Date |
Country |
WO 9531463 |
Nov 1995 |
WO |
WO 9822467 |
May 1998 |
WO |
Continuations (1)
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Number |
Date |
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Parent |
PCT/EP00/07585 |
Aug 2000 |
US |
Child |
10/076109 |
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