# US 12,109,209 B2 · Use of morphinan derivatives for treatment of opioid delta receptor agonist-related disease

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- Number: US 12,109,209 B2
- Document ID: US12109209B2
- Status: Granted
- Kind: B2
- Application number: 18/081,842
- Filed: 2022-12-15
- Published: 2023-04-27
- Granted: 2024-10-08
- Earliest claimed: 2016-09-16
- Assignees: Nippon Chemiphar Co., Ltd.
- Applicants: Nippon Chemiphar Co., Ltd.
- Inventors: Hiroshi Nagase; Hideaki Fujii; Akiyoshi Saitoh; Eriko Nakata; Masaaki Hirose; Isao Ooi; Kohei Hayashida
- Web page: https://patentgrep.com/patent/US12109209B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/497: containing further heterocyclic rings
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A method for therapeutic treatment of pain-associated anxiety or depression in a mammalian subject in need thereof, that includes administering to the subject an effective amount of a pharmaceutical composition containing a morphinan derivative that exhibits an opioid δ receptor agonist activity.

## Claims

### Claim 1

A method for therapeutic treatment of pain-associated anxiety or depression in a mammalian subject in need thereof, comprising:
administering to the subject an effective amount of a compound selected from the group consisting of:
2-((1S,3aR,5aS,6R,11bR, 11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridine 1-oxide;
3-((1S,3aR,5aS,6R,11bR, 11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridin-2(1H)-one;
6-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridin-2(1H)-one;
5-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)-1-methylpyridin-2(1H)-one;
6-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)-1-methylpyridin-2(1H)-one; and
6-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridazin-3(2H)-one;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the pain-associated anxiety or depression is fibromyalgia-associated anxiety or depression.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the compound is orally administered at a dose of 0.1-100 mg/day.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the compound is:
2-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridine 1-oxide, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the compound is:
3-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridin-2(1H)-one, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the compound is:
6-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridin-2(1H)-one, or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the compound is:
5-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)-1-methylpyridin-2(1H)-one, or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the compound is:
6-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)-1-methylpyridin-2(1H)-one, or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the compound is:
6-((1S,3aR,5aS,6R,11bR,11cS)-14-(cyclopropylmethyl)-10-hydroxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(epiminoethano)-1,5a-methanonaphtho[1,2-e]indole-3-carbonyl)pyridazin-3(2H)-one, or a pharmaceutically acceptable salt thereof.