Acrylamide-substituted indane compounds and therapeutic use thereof

Patent metadata

Field	Value
Publication number	US-12441679-B2
Application number	US-202118018459-A
Country	US
Kind code	B2
Filing date	Jul 29, 2021
Priority date	Jul 30, 2020
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

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

First claim

The invention claimed is:

1. 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.

2. The compound according to claim 1 , having formula (Ia)

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein R3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein:
R1 is an oxygen atom and R2 is chosen from:
a phenyl group unsubstituted or substituted with one or more R4 groups;
a (C4-C8) cycloalkyl group unsubstituted or substituted with one or more R5 groups; and
a (C1-C5) alkyl group substituted with one or more fluorine atoms;

or R1 is —N(H)— and R2 is chosen from:
a phenyl group unsubstituted or substituted with one or more R4 groups; and
a heteroaryl group unsubstituted or substituted with one or more R5 groups;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein:
R2 is chosen from:
a phenyl group unsubstituted or substituted with one or more R4 groups;
a (C4-C8) cycloalkyl group substituted with one or more R5 groups, provided that R1 is an oxygen atom; and
a (C1-C5) alkyl group substituted with one or more fluorine atoms, provided that R1 is an oxygen atom;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 5 , wherein R2 is a phenyl group substituted with one or more R4 groups;
or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 4 , wherein R4 is chosen from
a halogen atom; and
a (C1-C4) alkyl group unsubstituted or substituted with one or more fluorine atoms;

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 4 , wherein R4 is chosen from a fluorine atom and a trifluoromethyl group,
or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 4 , wherein the R4 group(s) is(are) in the meta and/or para position(s) of the R2 phenyl group,
or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 4 , wherein R5 is chosen from a fluorine atom and a trifluoromethyl group, or a pharmaceutically acceptable salt thereof.

11. 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)amin

Assignees

• Sanofi Sa

Inventors

• Fett Eykmar
• Venier Olivier

Classifications

• C07C2602/08

  the other ring being five-membered, e.g. indane · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D213/38

  having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom · CPC title

• C07C233/44

  having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton · CPC title