US 12,435,051 B2Granted

Dual modulator of mGluR5 and 5-HT2A receptor, and use thereof

AssigneeVivozon Inc.

InventorsDae Kyu Choi, Hyo Jin Kim, Mi Seon Bae, Jin Choi, Hyun Jin Heo, Yong Seok Lee, Geon Ho Lee, Mi Yon Shim, Jin Sun Park, Han Mi Lee

Life of this patent

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Abstract

Disclosed are a dual modulator of mGluR5 and 5-HT2AR (5-HT2A receptor), and use thereof. More specifically, disclosed are a compound which acts as modulator of mGluR5 and an antagonist of 5-HT2AR at the same time, and use thereof as therapeutic agent for pain.

Claims3

Dependent claims

A compound selected from the group consisting of:

N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide;
N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide;
N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide;
4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide;
N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide;
N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide;
methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate;
3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid;
4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide;
4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide;
methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate;
2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid;
4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide;
N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
and
N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide;
or a pharmaceutically acceptable salt thereof.

32 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/760,458Filed 1 Jul 2024 · continuation
Priority: KR 10-2020-009423629 Jul 2020
Published: US 2024/0360092 A131 Oct 2024
Granted: 7 Oct 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification31 codes

C07D 295/135
Substituted by singly or doubly bound nitrogen atoms: with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic…
A61K 31/4402
Non condensed pyridines; Hydrogenated derivatives thereof: only substituted in position 2, e.g. pheniramine, bisacodyl
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids
C07C 233/58
Having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings: having the nitrogen atoms of the…

Family

PCT/KR2021/009826Parent of this continuation · filed 28 Jul 2021
US 2024/0360092 A1Pre-grant publication · published 31 Oct 2024
Application17/631,212Parent of this continuation
US 12,060,339 B2Parent of this continuation
US 2022/0274939 A1Published application
US 12,435,051 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound selected from the group consisting of:

N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide;
N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide;
N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide;
N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide;
4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide;
N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide;
N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide;
methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate;
3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid;
4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide;
4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide;
methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate;
2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid;
4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide;
4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide;
N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide;
N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide;
and
N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide;
or a pharmaceutically acceptable salt thereof.

32 more elements

Facts

Application

18/760,458Filed 1 Jul 2024 · continuation

Priority

KR 10-2020-009423629 Jul 2020

Published

US 2024/0360092 A131 Oct 2024

Granted

7 Oct 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification31 codes

C07D 295/135
Substituted by singly or doubly bound nitrogen atoms: with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic…
A61K 31/4402
Non condensed pyridines; Hydrogenated derivatives thereof: only substituted in position 2, e.g. pheniramine, bisacodyl
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids
C07C 233/58
Having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings: having the nitrogen atoms of the…

Family

PCT/KR2021/009826Parent of this continuation · filed 28 Jul 2021

US 2024/0360092 A1Pre-grant publication · published 31 Oct 2024

Application17/631,212Parent of this continuation

US 12,060,339 B2Parent of this continuation

US 2022/0274939 A1Published application

US 12,435,051 B2This patent

From the US filing history. Foreign family members aren’t listed.