US 12,441,679 B2Granted

Acrylamide-substituted indane compounds and therapeutic use thereof

AssigneeSanofi

InventorsEykmar Fett, Olivier Venier

Life of this patent

Estimating the term…

Abstract

The invention relates to indane compounds of formula (I): to their preparation and to their therapeutic use.

Claims20

Dependent claims

A compound of formula (I)

wherein
R1 is chosen from:
an oxygen atom, and
a group —N(H)— or a group —N(R8)-,
wherein R8 is a (C1-C4) alkyl group;
R2 is chosen from:
a phenyl group unsubstituted or substituted with one or more R4 groups;
a benzyl group unsubstituted or substituted with one or more R5 groups;
a (C4-C8) cycloalkyl group unsubstituted or substituted with one or more R5 groups;
a heteroaryl group unsubstituted or substituted with one or more R5 groups;
and
a (C1-C6) alkyl group substituted with one or more fluorine atoms;
R4 is chosen from:
a halogen atom;
a (C1-C4) alkyl group unsubstituted or substituted with one or more fluorine atoms;
a (C1-C4) alkoxy group unsubstituted or substituted with one or more fluorine atoms;
a C(O)—O—(C1-C4) alkyl group;
a (C3-C6) cycloalkyl group;
a (C1-C4) alkylthio group;
and
a pentafluorosulfanyl group;
R5 is chosen from:
a halogen atom;
and
a (C1-C4) alkyl group unsubstituted or substituted with one or more fluorine atoms;
R3 is chosen from:
a hydrogen atom, and
a (C1-C4) alkyl group;
R6 is chosen from a hydrogen atom or a halogen atom;
R7 is independently chosen from:
a halogen atom;
a (C1-C4) alkyl group;
a hydroxy group;
and
a (C1-C4) alkoxy group;
and
n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

35 more elements

A compound selected from:

N-(1-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(1-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(S)—N-(1-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-methyl-N-(1-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((4-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(S)—N-(1-((4-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(1-((4-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((3-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((3,5-difluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((3,4-difluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((3-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((4-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((3,4-difluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((3-methoxyphenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(m-tolylamino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((6-fluoropyridin-3-yl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((6-(trifluoromethyl)pyridin-3-yl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((5-fluoropyridin-2-yl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
methyl-3-((5-acrylamido-2,3-dihydro-1H-inden-1-yl)amino)benzoate;
N-(3-(benzylamino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((3-(trifluoromethyl)benzyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((4-(trifluoromethyl)benzyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-(((cis)-4-(trifluoromethyl)cyclohexyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-(((trans)-4-(trifluoromethyl)cyclohexyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-((4,4-difluorocyclohexyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-((4,4,4-trifluorobutyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-((3-fluoropropyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-((3-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(2-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(4,4,4-trifluorobutoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(4-fluorobutoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((4,4-difluorocyclohexyl)oxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(4-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-phenoxy-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3,4-difluorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3-fluorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(4-fluorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3,5-difluorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(2,4-difluorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(3-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(3-(trifluoromethoxy)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
methyl 3-[6-(prop-2-enoylamino)-2,3-dihydro-1H-1-yl]oxybenzoate;
(S)—N-(2-((3-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(2-((3-fluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(2-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(S)—N-(2-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[2-[4-(trifluoromethyl)anilino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-(3-((3,5-difluorophenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((3-(pentafluoro-16-sulfanyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(1-((4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(S)—N-(1-((4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[(1S)-1-[[4-(trifluoromethyl)pyridine-2-yl]amino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-[(1R)-1-[[4-(trifluoromethyl)pyridin-2-yl]amino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-(1-((4-(trifluoromethyl)pyridin-2-yl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide 2,2,2-trifluoroacetate;
N-(1-((6-(trifluoromethyl)pyridin-2-yl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-((5-(trifluoromethyl)pyridin-3-yl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(methyl(3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(methyl(phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(methyl(4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3,3-dimethyl-1-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3,3-dimethyl-1-((4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[7-fluoro-1-[3-(trifluoromethyl)anilino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-[4-fluoro-1-[4-(trifluoromethyl)anilino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-methyl-N-(1-((4-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((4,4-difluorocyclohexyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((3-(trifluoromethyl)cyclopentyl)oxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-((5,5,5-trifluoropentyl)oxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(4,4-difluorobutoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(2,2,2-trifluoroethoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3,3,3-trifluoropropoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-methyl-N-(1-((4-(trifluoromethyl)cyclohexyl)oxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(4-chlorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3-chlorophenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(m-tolyloxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3-(methylthio)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(3-(3-cyclopropylphenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-(1-(4-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-methyl-N-(1-(4-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(S)—N-(1-(3-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(1-(3-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(S)—N-(3-(4-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
(R)—N-(3-(4-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[3-[[5-(trifluoromethyl)pyridin-2-yl]oxy]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-methyl-N-(1-(3-(trifluoromethyl)phenoxy)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[2-fluoro-3-[4-(trifluoromethyl)anilino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-(2-fluoro-3-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[2-fluoro-3-[4-(trifluoromethyl)phenoxy]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-methyl-N-(2-methyl-1-((3-(trifluoromethyl)phenyl)amino)-2,3-dihydro-1H-inden-5-yl)acrylamide;
N-[(cis)-3-methoxy-1-[3-(trifluoromethyl)anilino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
N-[(trans)-2-hydroxy-1-[3-(trifluoromethyl)anilino]2,3-dihydro-1H-inden-5-yl]acrylamide;
N-[rac-(2R,3R)-2-hydroxy-3-[3-(trifluoromethyl)anilino]-2,3-dihydro-1H-inden-5-yl]acrylamide;
and the pharmaceutically acceptable salts thereof.

94 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/018,459Filed 29 Jul 2021
Priority: EP 2030587630 Jul 2020
Published: US 2023/0265047 A124 Aug 2023
Granted: 14 Oct 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07C 233/09
Having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals: with carbon atoms of…
C07D 213/36
With substituted hydrocarbon radicals attached to ring carbon atoms: radicals substituted by singly-bound nitrogen atoms
A61P 35/00
Antineoplastic agents
C07C 233/27
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring:…

Family

US 2023/0265047 A1Pre-grant publication · published 24 Aug 2023
US 12,441,679 B2This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Facts

Application

18/018,459Filed 29 Jul 2021

Priority

EP 2030587630 Jul 2020

Published

US 2023/0265047 A124 Aug 2023

Granted

14 Oct 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07C 233/09
Having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals: with carbon atoms of…
C07D 213/36
With substituted hydrocarbon radicals attached to ring carbon atoms: radicals substituted by singly-bound nitrogen atoms
A61P 35/00
Antineoplastic agents
C07C 233/27
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring:…