US 2019/0194178 A1Published application

Substituted ureas and methods of making and using same

AssigneeMebias Discovery, Inc.

InventorsBRETT A. TOUNGE, SHARIFF BAYOUMY, LAWRENCE C. KUO, SCOTT DAX

Life of this patent

Estimating the term…

Abstract

The invention relates to substituted ureas, and compositions comprising the same, which in certain embodiments are useful for treating and/or preventing pain in a subject in need thereof.

Claims21

Dependent claims

A compound of formula (I), or a salt, solvate, enantiomer, diastereoisomer or tautomer thereof:

wherein:
A is selected from the group consisting of
B1 is selected from the group consisting of
and B2 is H;
or
B1 and B2 are independently selected from the group consisting of —CH3 and —CH2CH3, or
B1 and B2 combine to form a divalent substituent selected from the group consisting of —CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2—, and —CH2CH2OCH2CH2—;
R1 and R2 are independently selected from the group consisting of H, CH3, and CH3 substituted with at least one selected from the group consisting of fluoro, chloro, cyano, hydroxyl and nitro;
R3 is selected from the group consisting of H and CH3;
X is selected from the group consisting of S, O, and N-R3;
R3 is selected from the group consisting of hydrogen, alkyl and substituted alkyl;
each occurrence of R is independently selected from the group consisting of fluoro, chloro, bromo, iodo, cyano, nitro, hydroxyl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, and substituted phenyl;
each occurrence of m is independently selected from the group consisting of 0, 1, 2 and 3;
n is selected from the group consisting of 1, 2 and 3;
and
each occurrence of p is independently selected from the group consisting of 0, 1, 2 and 3.

13 more elements

A compound, or a salt, solvate, enantiomer, diastereoisomer or tautomer thereof, selected from the group consisting of:

N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-isoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5-fluoroisoindoline-2-carboxamide;
(−)-ent-N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5-fluoroisoindoline-2-carboxamide;
(+)-ent-N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5-fluoroisoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-4-fluoroisoindoline-2-carboxamide;
5-Chloro-N-(2-(dimethylamino)-2-(thiophen-3-yl)ethyl)isoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5-methoxyisoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5,6-difluoroisoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-6-fluoro-3,4-dihydroquinoline-1(2H)-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-7-fluoro-3,4-dihydroquinoline-1(2H)-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-3,4-dihydroquinoline-1(2H)-carboxamide;
1-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-3-(1,2,3,4-tetrahydronaphthalen-2-yl)urea;
1-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-3-(1,2,3,4-tetrahydronaphthalen-1-yl)urea;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5-methylisoindoline-2-carboxamide;
3-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-1-methyl-1-(1,2,3,4-tetrahydronaphthalen-1-yl)urea;
N-(2-(2-Chloro-4-fluorophenyl)-2-(dimethylamino)ethyl)isoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(4-methoxyphenyl)ethyl)isoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(4-methoxyphenyl)ethyl)-5-fluoroisoindoline-2-carboxamide;
N-(2-(2-Chloro-4-fluorophenyl)-2-(dimethylamino)ethyl)-5-fluoroisoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-phenylethyl)isoindoline-2-carboxamide;
1-(2-(Dimethylamino)-2-phenylethyl)-3-(1,2,3,4-tetrahydronaphthalen-2-yl)urea;
N-(2-(Dimethylamino)-2-phenylethyl)-5-fluoroisoindoline-2-carboxamide;
3-(2-Dimethylamino-2-thiophen-3-yl-ethyl)-1-methyl-1-(S)-1,2,3,4-tetrahydro-naphthalen-1-yl-urea;
(R)-3-Phenyl-pyrrolidine-1-carboxylic acid (2-dimethylamino-2-thiophen-3-yl-ethyl)-amide;
(S)-3-Phenyl-pyrrolidine-1-carboxylic acid (2-dimethylamino-2-thiophen-3-yl-ethyl)-amide;
(S)-3-Phenyl-pyrrolidine-1-carboxylic acid [2-dimethylamino-2-(4-methoxy-phenyl)-ethyl]-amide;
(R)-3-Phenyl-pyrrolidine-1-carboxylic acid [2-dimethylamino-2-(4-methoxy-phenyl)-ethyl]-amide;
4-Cyano-1,3-dihydro-isoindole-2-carboxylic acid (2-dimethylamino-2-thiophen-3-yl-ethyl)-amide;
3-(2-Dimethylamino-2-thiophen-3-yl-ethyl)-1-methyl-1-(R)-1,2,3,4-tetrahydro-naphthalen-1-yl-urea;
5-Fluoro-1,3-dihydro-isoindole-2-carboxylic acid (1-dimethylamino-cyclohexylmethyl)-amide hydrochloride;
1-(2-Dimethyl amino-2-thiophen-3-yl-ethyl)-3-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-urea-;
7-Hydroxy-3,4-dihydro-2H-quinoline-1-carboxylic acid (2-dimethylamino-2-thiophen-3-yl-ethyl)-amide;
1-(2-Dimethyl amino-2-thiophen-3-yl-ethyl)-3-((R)-7-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-urea;
1-(2-Dimethyl amino-2-thiophen-3-yl-ethyl)-3-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-urea;
1-(2-Dimethyl amino-2-thiophen-3-yl-ethyl)-3-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-urea;
6-Hydroxy-3,4-dihydro-2H-quinoline-1-carboxylic acid (2-dimethylamino-2-thiophen-3-yl-ethyl)-amide;
1,3-Dihydro-isoindole-2-carboxylic acid (1-dimethylamino-cyclohexylmethyl)-amide;
(R)-1-((1-(Dimethylamino)cyclohexyl)methyl)-3-(1,2,3,4-tetrahydronaphthalen-2-yl)urea;
(S)-1-((1-(Dimethyl amino)cyclohexyl)methyl)-3-(1,2,3,4-tetrahydronaphthalen-2-yl)urea;
(−)-N-(2-(Dimethylamino)-2-phenylethyl)isoindoline-2-carboxamide;
(+)-N-(2-(Dimethylamino)-2-phenylethyl)isoindoline-2-carboxamide;
1-(2-Dimethyl amino-2-thiophen-3-yl-ethyl)-3-(5-hydroxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea;
1-(2-Dimethylamino-2-thiophen-3-yl-ethyl)-3-((S)-7-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-urea;
5-Fluoro-1,3-dihydro-isoindole-2-carboxylic acid (4-dimethylamino-tetrahydro-pyran-4-ylmethyl)-amide;
5-Fluoro-1,3-dihydro-isoindole-2-carboxylic acid (2-dimethylamino-2-methyl-propyl)-amide;
5-Fluoro-1,3-dihydro-isoindole-2-carboxylic acid (1-dimethylamino-cyclopentylmethyl)-amide;
1,3-Dihydro-isoindole-2-carboxylic acid (1-dimethylamino-cyclopentylmethyl)-amide;
1-(1-Dimethylamino-cyclopentylmethyl)-3-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-urea;
1-(2-Dimethylamino-2-thiophen-3-yl-ethyl)-3-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-urea;
1-(2-Dimethylamino-2-thiophen-3-yl-ethyl)-3-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-urea;
N-(2-(Dimethylamino)-2-(4-methoxyphenyl)ethyl)-6-fluoro-3,4-dihydroquinoline-1(2H)-carboxamide;
N-(2-(Dimethylamino)-2-phenylethyl)-3,4-dihydroquinoline-1(2H)-carboxamide;
N-(2-(Dimethylamino)-2-phenylethyl)-6-fluoro-3,4-dihydroquinoline-1(2H)-carboxamide;
1-((R)-3-(dimethylamino)-3-(thiophen-3-yl)propyl)-3-((R)-1,2,3,4-tetrahydronaphthalen-2-yl)urea;
1-((R)-3-(dimethylamino)-3-(thiophen-3-yl)propyl)-3-((S)-1,2,3,4-tetrahydronaphthalen-2-yl)urea;
1-((S)-3-(dimethylamino)-3-(thiophen-3-yl)propyl)-3-((R)-1,2,3,4-tetrahydronaphthalen-2-yl)urea;
1-((S)-3-(dimethylamino)-3-(thiophen-3-yl)propyl)-3-((S)-1,2,3,4-tetrahydronaphthalen-2-yl)urea;
(R)-N-((R)-3-(Dimethylamino)-3-(thiophen-3-yl)propyl)-3-phenylpyrrolidine-1-carboxamide;
(S)-N-((R)-3-(Dimethylamino)-3-(thiophen-3-yl)propyl)-3-phenylpyrrolidine-1-carboxamide;
(S)-N-((S)-3-(Dimethylamino)-3-(thiophen-3-yl)propyl)-3-phenylpyrrolidine-1-carboxamide;
(−)-N-(2-(Methylamino)-2-(thiophen-3-yl)ethyl)isoindoline-2-carboxamide;
(+)-N-(2-(Methylamino)-2-(thiophen-3-yl)ethyl)isoindoline-2-carboxamide;
(−)-4-Fluoro-N-(2-(methylamino)-2-(thiophen-3-yl)ethyl)isoindoline-2-carboxamide;
(+)-4-Fluoro-N-(2-(methylamino)-2-(thiophen-3-yl)ethyl)isoindoline-2-carboxamide;
(−)-5-Fluoro-N-(2-(4-methoxyphenyl)-2-(methylamino)ethyl)isoindoline-2-carboxamide;
(+)-5-Fluoro-N-(2-(4-methoxyphenyl)-2-(methylamino)ethyl)isoindoline-2-carboxamide;
(R)-N-(3-(Dimethylamino)-3-(thiophen-3-yl)propyl)-5-fluoroisoindoline-2-carboxamide;
(S)-N-(3-(Dimethylamino)-3-(thiophen-3-yl)propyl)-5-fluoroisoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(4-hydroxyphenyl)ethyl)-5-fluoroisoindoline-2-carboxamide;
N-(2-(Dimethylamino)-2-(thiophen-3-yl)ethyl)-5-hydroxyisoindoline-2-carboxamide;
N-(2-(dimethylamino)-2-(4-hydroxyphenyl)ethyl)-5-hydroxyisoindoline-2-carboxamide;
5-Fluoro-N-(2-(methylamino)-2-(thiophen-3-yl)ethyl)isoindoline-2-carboxamide;
N-(2-(Methylamino)-2-phenylethyl)isoindoline-2-carboxamide;
(−)-N-(2-(Methylamino)-2-phenylethyl)isoindoline-2-carboxamide;
and
(+)-N-(2-(Methylamino)-2-phenylethyl)isoindoline-2-carboxamide.

73 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/329,984Filed 31 Aug 2017
Priority: 1 Sep 2016
Published: 27 Jun 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07D 409/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07C 273/18
Preparation of urea or its derivatives, i.e. compounds containing any of the groups [IMAGE cpc-sch-C07C-0967.gif] , the nitrogen atoms not being…:…
C07C 275/06
Having nitrogen atoms of urea groups bound to acyclic carbon atoms: of an acyclic and saturated carbon skeleton

Family

Application62/382,530Us provisional application · filed 1 Sep 2016
US 10,683,283 B2Related patent
US 2019/0194178 A1This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

The invention relates to substituted ureas, and compositions comprising the same, which in certain embodiments are useful for treating and/or preventing pain in a subject in need thereof.

Facts

Application

16/329,984Filed 31 Aug 2017

Priority

1 Sep 2016

Published

27 Jun 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07D 409/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07C 273/18
Preparation of urea or its derivatives, i.e. compounds containing any of the groups [IMAGE cpc-sch-C07C-0967.gif] , the nitrogen atoms not being…:…
C07C 275/06
Having nitrogen atoms of urea groups bound to acyclic carbon atoms: of an acyclic and saturated carbon skeleton