US 12,624,004 B2Granted

Opioid receptor agonist, preparation method therefor and pharmaceutical use thereof

AssigneeFudan University

InventorWei Fu

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Abstract

The invention belongs to the field of pharmacy, and relates to a class of opioid receptor agonists, their preparation method and the pharmaceutical use thereof, in particular to 3-(dimethylaminomethyl) cyclohex-4-ol derivatives or salts thereof and preparation method thereof, 3-(dimethylaminomethyl) piperidin-4-ol derivatives or salts thereof and preparation method thereof, 3-(dimethylaminomethyl) piperidin-4-ol derivatives or salts thereof and preparation method thereof, 3-(dimethylaminomethyl) piperidin-4-ol derivative or salt thereof and preparation method thereof, 3-(dimethylaminomethyl) piperidin-4-ol derivative or salt thereof and preparation method thereof, and relate to the use of said compounds in the treatment of opioid receptor-mediated diseases. The use of the compound or pharmaceutically acceptable salt, solvate or hydrate thereof in the preparation of a medicament for treating indications related to opioid receptors. The opioid receptor-related indications are pain, irritable bowel syndrome, pruritus, addiction and depression.

A compound or pharmaceutically acceptable salt thereof selected from:

2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-(phenylsulfonyl)cyclohexyl benzoate;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) benzenesulfonamide;
4-((3-chlorophenyl) sulfonamido)-2-((dimethylamino) methyl)-1-(3-methoxyphenyl) cyclohexyl benzoate;
3-chloro-N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) benzenesulfonamide;
2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-(thiophene-2-sulfonamido) cyclohexyl benzoate;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) thiophene-2-sulfonamide;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) thiophene-2-sulfonamide;
2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-((phenylmethyl) sulfonamido) cyclohexyl benzoate;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl)-1-benzenesulfonamide hydrochloride;
4-(((3-chlorophenyl)methyl) sulfonamido)-2-((dimethylamino) methyl)-1-(3-methoxyphenyl) cyclohexyl benzoate;
1-(3-chlorophenyl)-N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) methanesulfonamide;
2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-(N-methylbenzenesulfonamido) cyclohexyl benzoate;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl)-N-methylbenzenesulfonamide;
4-((3-chloro-N-methylphenyl) sulfonamido)-2-((dimethylamino) methyl)-1-(3-methoxyphenyl) cyclohexyl benzoate;
3-chloro-N-(3-((dimethylamino) methyl)-4-hydroxy-4-(methoxyphenyl) cyclohexyl)-N-methylbenzenesulfonamide;
2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-(N-methylthiophene-2-sulfonamido) cyclohexyl benzoate;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl)-N-methylthiophene-2-sulfonamide;
2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-((N-methyl-1-benzyl) sulfonamido) cyclohexyl benzoate;
N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl)-N-methyl-1-phenylmethanesulfonamide;
4-((1-(3-chlorophenyl)-N-methyl) sulfonamido)-2-((dimethylamino) methyl)-1-(3-methoxyphenyl) cyclohexyl benzoate;
N-benzyl-N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) benzenesulfonamide;
N-benzyl-3-chloro-N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) benzenesulfonamide;
N-benzyl-N-(3-((dimethylamino) methyl)-4-hydroxy-4-(3-methoxyphenyl) cyclohexyl) thiophene-2-sulfonamide;
4-(benzylsulfonyl)-2-((dimethylamino) methyl)-1-(3-methoxyphenyl) cyclohexan-1-ol;
and
2-((dimethylamino) methyl)-1-(3-methoxyphenyl)-4-((phenylsulfonyl) methyl) cyclohex-1-ol.

23 more elements

Facts

Application

17/755,780Filed 2 Nov 2020

Priority

CN 201911076305.X6 Nov 2019

Published

US 2023/0027752 A126 Jan 2023

Granted

12 May 2026

Term ends

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Classification15 codes

C07D 211/96
With a hetero atom directly attached to the ring nitrogen atom: sulfur atom
A61K 31/145
Amines: having sulfur, e.g. thiurams , Sulfinylamines , Sulfonylamines
A61K 31/4418
Non condensed pyridines; Hydrogenated derivatives thereof: having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids

Abstract

Claims5