US 2024/0116845 A1Published application

Indene compounds, pharmaceutical compositions thereof, and their therapeutic applications

AssigneeNucMito Pharmaceuticals Co. Ltd.

InventorsYing Su, Ziwen Chen, Haishan Wang

Life of this patent

Estimating the term…

Abstract

Provided herein are an indene compound, e.g., a compound of Formula (I), and a pharmaceutical composition thereof. Also provided herein is a method of their use for treating, preventing, or ameliorating one or more symptoms of a fibrotic disease.

Claims65

Dependent claims

A compound of Formula (I):

or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof;
wherein:
R1 is (a) hydrogen, deuterium, cyano, halo, or nitro;
or (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
R2, RA, and X are (i), (ii), or (iii):
(i) X is C1-6 alkylene, —N(RX)—C1-6 alkylene, —O—C1-6 alkylene, —S—C1-6 alkylene, —S(O)—C1-6 alkylene, or —S(O)2—C1-6 alkylene;
R2 is —C(O)OR2a, —C(O)NR2bR2c, —C(O)N(R2b)OR2c, or heteroaryl;
wherein each R2a, R2b, and R2c is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and
RA is C6-14 arylene or heteroarylene;
(ii) X is —N(RX)—, —O—, —S—, —S(O)—, or —S(O)2—;
R2 is —C(O)N(R2b)OR2c;
wherein R2b is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and R2c is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 to cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and
RA is C6-14 arylene or heteroarylene;
or
(iii) X is —N(RX)—, —O—, —S—, —S(O)—, or —S(O)2—;
R2 is —C(O)OR2a, —C(O)NR2bR2c, —C(O)N(R2b)OR2c, or heteroaryl;
wherein each R21, R2b, and R2c is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and
RA is C9-14 arylene or bicyclic heteroarylene;
R3, R4, R5, and R6 are each independently (a) hydrogen, deuterium, cyano, halo, or nitro;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or (c) —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(NR1a)NR1bR1c, —OS(O)R1a, —OS(O)2R1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)NR1bR1c, —NR1aC(NR1d)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
RB is C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
each RX is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
L is C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, or heterocyclylene;
and
each R1a, R1b, R1c, and R1d is independently hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or R1a and R1c together with the C and N atoms to which they are attached form heterocyclyl;
or R1b and R1c together with the N atom to which they are attached form heterocyclyl;
wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from:
(a) deuterium, cyano, halo, nitro, and oxo;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
and (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(O)SRa, —C(NRa)NRbRc, —C(S)Ra, —C(S)ORa, —C(S)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(O)SRa, —OC(NRa)NRbRc, —OC(S)Ra, —OC(S)ORa, —OC(S)NRbRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(O)SRd, —NRaC(NRd)NRbRc, —NRaC(S)Rd, —NRaC(S)ORd, —NRaC(S)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen or deuterium;
(ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
wherein each Qa is independently selected from:
(a) deuterium, cyano, halo, nitro, and oxo;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl;
and (c) —C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(O)SRe, —C(NC)NRfRg, —C(S)Re, —C(S)ORe, —C(S)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(O)SRe, —OC(NRC)NRfRg, —OC(S)Re, —OC(S)ORe, —OC(S)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NReC(O)Rh, —NReC(O)ORf, —NReC(O)NRfRg, —NReC(O)SRf, —NReC(NRh)NRfRg, —NReC(S)Rh, —NReC(S)ORf, —NReC(S)NRfRg, —NReS(O)Rh, —NReS(O)2Rh, —NReS(O)NRfRg, —NReS(O)2NRfRg, —SRe, —S(O)Re, —S(O)2Re, —S(O)NRfRg, and —S(O)2NRfRg;
wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen or deuterium;
(ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or (iii) Rf and Rg together with the N atom to which they are attached form heterocyclyl.

43 more elements

A compound of Formula (I):

or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof;
wherein:
R1 is (a) hydrogen, deuterium, cyano, halo, or nitro;
or (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
R2 is —C(O)OR2a, —C(O)NR2bR2c, —C(O)N(R2b)OR2c, or heteroaryl;
wherein R2a, R2b, and R2c are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
R3, R4, R5, and R6 are each independently (a) hydrogen, deuterium, cyano, halo, or nitro;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or (c) —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(NR1a)NR1bR1c, —OS(O)R1a, —OS(O)2R1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)NR1bR1c, —NR1aC(NR1d)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
RA is C6-14 arylene or heteroarylene;
RB and X are (i), (ii), or (iii):
(i) X is a bond, —O—, —S—, —S(O)—, or —S(O)2—;
and
RB is C3-10 cycloalkyl or heterocyclyl;
(ii) X is —O—, —S—, —S(O)—, or —S(O)2—;
and
RB is C6-14 aryl or heteroaryl;
(iii) X is —N(RX)—;
RB is C6-14 aryl or heteroaryl;
and
RX is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or
(iv) X is —N(RX)—;
and
RB and RX together with the N atom to which they are attached form heteroaryl or heterocyclyl;
L is C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, or heterocyclylene;
and
each R1a, R1b, R1c, and R1d is independently hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or R1a and R1c together with the C and N atoms to which they are attached form heterocyclyl;
or R1b and R1c together with the N atom to which they are attached form heterocyclyl;
wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from:
(a) deuterium, cyano, halo, nitro, and oxo;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
and (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(O)SRa, —C(NRa)NRbRc, —C(S)Ra, —C(S)ORa, —C(S)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(O)SRa, —OC(NRa)NRbRc, —OC(S)Ra, —OC(S)ORa, —OC(S)NRbRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(O)SRd, —NRaC(NRd)NRbRc, —NRaC(S)Rd, —NRaC(S)ORd, —NRaC(S)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen or deuterium;
(ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
wherein each Qa is independently selected from:
(a) deuterium, cyano, halo, nitro, and oxo;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl;
and (c) —C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(O)SRe, —C(NRe)NRfRg, —C(S)Re, —C(S)ORe, —C(S)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(O)SRe, —OC(NR)NRfRg, —OC(S)Re, —OC(S)ORe, —OC(S)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NReC(O)Rh, —NReC(O)ORf, —NReC(O)NRfRg, —NReC(O)SRf, —NReC(NRh)NRfRg, —NReC(S)Rh, —NReC(S)ORf, —NReC(S)NRfRg, —NReS(O)Rh, —NReS(O)2Rh, —NReS(O)NRfRg, —NRCS(O)2NRfRg, —SRe, —S(O)Re, —S(O)2Re, —S(O)NRfRg, and —S(O)2NRfRg;
wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen or deuterium;
(ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or (iii) Rf and Rg together with the N atom to which they are attached form heterocyclyl.

41 more elements

A compound selected from:

2-[(1Z)-5-fluoro-1-(4-((4-fluorophenoxy)methyl)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid A1;
2-[(1Z)-5-fluoro-1-(4-(benzyloxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid A2;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-fluorobenzyl]phenyl}methylidene)-1H-inden-3-yl]acetic acid A3;
2-[(1Z)-5-fluoro-1-(3-(benzyloxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid A4;
(Z)-2-(5-fluoro-2-methyl-1-(3-(phenoxymethyl)benzylidene)-1H-inden-3-yl)acetic acid A5;
2-[(1Z)-5-fluoro-1-({3-[(4-fluorophenoxy)methyl]phenyl}methylidene)-2-methyl-1H-inden-3-yl]acetic acid A6;
2-[(1Z)-1-{[2-(benzyloxy)-4-fluorophenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A7;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(2-phenylethyl)phenyl]methylidene}-1H-inden-3-yl]acetic acid A8;
2-[(1Z)-5-fluoro-2-methyl-1-[(4-{[methyl(phenyl)amino]methyl}phenyl)-methylidene]-1H-inden-3-yl]acetic acid A9;
2-[(1Z)-1-[(4-{[benzyl(phenyl)amino]methyl}phenyl)methylidene]-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A10;
2-[(1Z)-4-methoxy-1-(4-((phenoxy)methyl)benzylidene)-1H-inden-3-yl]-acetic acid A11;
(Z)-2-(6-methoxy-2-methyl-1-(4-(phenoxymethyl)benzylidene)-1H-inden-3-yl)acetic acid A12;
2-[(1Z)-6-methoxy-2-methyl-1-[(4-{[methyl(phenyl)amino]methyl}phenyl)-methylidene]-1H-inden-3-yl]acetic acid A13;
2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenoxy)methyl]-2-(trifluoromethyl)phenyl}-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A14;
2-[(1Z)-1-({4-[(2,4-difluorophenoxy)methyl]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A15;
2-[(1Z)-5-fluoro-2-methyl-1-[(3-{[methyl(phenyl)amino]methyl}phenyl)-methylidene]-1H-inden-3-yl]acetic acid A16;
2-[(1Z)-5-fluoro-2-methyl-1-{[3-(2-phenylethyl)phenyl]methylidene}-1H-inden-3-yl]acetic acid A17;
2-[(1Z)-5-fluoro-2-methyl-1-[(3-methyl-5-{[methyl(phenyl)amino]methyl}-phenyl)methylidene]-1H-inden-3-yl]acetic acid A18;
2-[(1Z)-1-({3-[(2,4-difluorophenoxy)methyl]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A19;
2-[(1Z)-1-({3-[(3,4-difluorophenoxy)methyl]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A20;
2-[(1Z)-5-fluoro-2-methyl-1-[(3-{[4-(trifluoromethyl)phenoxy]methyl}phenyl)-methylidene]-1H-inden-3-yl]acetic acid A21;
2-[(1Z)-1-({3-[(4-tert-butylphenoxy)methyl]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A22;
2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]-N-hydroxy-N-methylacetamide B1;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxy-N-methylacetamide B2;
(Z)-2-(1-(4-cyclopropylbenzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)-N-hydroxy-N-methylacetamide B3;
(Z)-2-(1-(4-(tert-butyl)benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)-N-methoxy-N-methylacetamide B4;
(Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)-N-hydroxy-N-methylacetamide B5;
(Z)-2-(5-fluoro-2-methyl-1-((4-methylnaphthalen-1-yl)methylene)-1H-inden-3-yl)-N-hydroxy-N-methylacetamide C1;
(Z)-2-(5-fluoro-2-methyl-1-((4-methylnaphthalen-1-yl)methylene)-1H-inden-3-yl)-N-hydroxyacetamide C2;
(Z)-2-(1-((4-bromonaphthalen-1-yl)methylene)-5-fluoro-2-methyl-1H-inden-3-yl)acetic acid C3;
(Z)-2-(1-((4-bromonaphthalen-1-yl)methylene)-5-fluoro-2-methyl-1H-inden-3-yl)-N-hydroxyacetamide C4;
(Z)-2-(5-fluoro-2-methyl-1-(quinolin-4-ylmethylene)-1H-inden-3-yl)acetic acid C5;
(Z)-2-(5-fluoro-2-methyl-1-(quinolin-4-ylmethylene)-1H-inden-3-yl)-N-hydroxyacetamide C6;
(Z)-2-(5-fluoro-2-methyl-1-((5,6,7,8-tetrahydronaphthalen-1-yl)methylene)-1H-inden-3-yl)acetic acid C7;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]-N-hydroxyacetamide D1;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(tert-butyl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D2;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-(tert-butyl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D3;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-fluoro-4-methylphenoxy]phenyl}-methylidene)-1H-inden-3-yl]acetic acid D4;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[3,4-difluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D5;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-nitrophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D6;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(trifluoromethyl)phenoxy]phenyl}-methylidene)-1H-inden-3-yl]acetic acid D7;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-(2-methyl-propyl)-1H-inden-3-yl]acetic acid D8;
2-[(1Z)-5-fluoro-2-benzyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D9;
2-[(1Z)-5-methoxy-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D10;
2-[(1Z)-5-methoxy-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]acetic acid D11;
2-[(1Z)-1-{[2-trifluoromethyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid D12;
2-[(1Z)-1-{[3-methyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid D13;
2-[(1Z)-1-{[2-methyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid D14;
2-[(1Z)-5,7-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D15;
2-[(1Z)-4,6-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D16;
2-[(1Z)-5-tert-butyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D17;
(Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)acetic acid D18;
2-[(1Z)-5-fluoro-1-(2-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D19;
2-[(1Z)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D20;
2-[(1Z)-4,6-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D21;
2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-methoxyphenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D22;
2-[(1Z)-5-fluoro-1-(4-fluoro-3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D23;
2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-cyanophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D24;
2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-chlorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid D25;
2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-trifluoromethylphenoxy]phenyl}-methylidene)-1H-inden-3-yl]acetic acid D26;
2-[(1Z)-5-fluoro-2-methyl-1-({3-[3-trifluoromethylphenoxy]phenyl}-methylidene)-1H-inden-3-yl]acetic acid D27;
2-[(1Z)-4-methoxy-1-(4-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D28;
2-[(1Z)-6-methoxy-1-(4-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D29;
2-[(1Z)-6-trifluoromethyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}-methylidene)-1H-inden-3-yl]acetic acid D30;
2-[(1Z)-5-trifluoromethyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}-methylidene)-1H-inden-3-yl]acetic acid D31;
2-[(1Z)-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid D32;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid D33;
2-[(1Z)-5-trifluoromethyl-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D34;
2-[(1Z)-6-methoxy-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D35;
2-[(1Z)-6-trifluoromethyl-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid D36;
2-[(1Z)-5-fluoro-2-methyl-1-({3-[methyl(phenyl)amino]phenyl}methylidene)-1H-inden-3-yl]acetic acid D37;
2-[(1Z)-5-fluoro-1-[(3-methoxy-5-phenoxyphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid D38;
(Z)-2-(1-(4-(cyclopent-1-en-1-yl)benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)acetic acid D39;
(Z)-2-(1-(4-(cyclopent-1-en-1-yl)benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)-N-hydroxyacetamide D40;
(Z)-2-(1-(4-(tert-butyl)benZylidene)-5-fluoro-2-methyl-1H-inden-3-yl)acetamide D41;
(Z)-2-(1-(4-(tert-butyl)benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)-N-hydroxyacetamide D42;
2-[(1E)-5-fluoro-2-methyl-1-({4-[3,4-difluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid E1;
2-[(1E)-5-fluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid E2;
2-[(1E)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]acetic acid E3;
2-[(1E)-5,7-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid E4;
5-{2-[(1E)-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole E5;
(E)-2-(1-(4-(tert-butyl)benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)-N-hydroxyacetamide E6;
and
2-[(1E)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid E7;
and tautomers, mixtures of two or more tautomers, and isotopic variants thereof, and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof.

82 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/505,975Filed 9 Nov 2023
Priority: WO PCT/CN2021/09397515 May 2021
Published: 11 Apr 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07C 62/14
Polycyclic: having a carboxyl group on a condensed ring system
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 21/00
Drugs for disorders of the muscular or neuromuscular system
A61P 35/00
Antineoplastic agents

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Application18/505,975Continuation
US 2024/0116845 A1This patent

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

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Abstract

A compound of Formula (I):

or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof;
wherein:
R1 is (a) hydrogen, deuterium, cyano, halo, or nitro;
or (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
R2, RA, and X are (i), (ii), or (iii):
(i) X is C1-6 alkylene, —N(RX)—C1-6 alkylene, —O—C1-6 alkylene, —S—C1-6 alkylene, —S(O)—C1-6 alkylene, or —S(O)2—C1-6 alkylene;
R2 is —C(O)OR2a, —C(O)NR2bR2c, —C(O)N(R2b)OR2c, or heteroaryl;
wherein each R2a, R2b, and R2c is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and
RA is C6-14 arylene or heteroarylene;
(ii) X is —N(RX)—, —O—, —S—, —S(O)—, or —S(O)2—;
R2 is —C(O)N(R2b)OR2c;
wherein R2b is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and R2c is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 to cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and
RA is C6-14 arylene or heteroarylene;
or
(iii) X is —N(RX)—, —O—, —S—, —S(O)—, or —S(O)2—;
R2 is —C(O)OR2a, —C(O)NR2bR2c, —C(O)N(R2b)OR2c, or heteroaryl;
wherein each R21, R2b, and R2c is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
and
RA is C9-14 arylene or bicyclic heteroarylene;
R3, R4, R5, and R6 are each independently (a) hydrogen, deuterium, cyano, halo, or nitro;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or (c) —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(NR1a)NR1bR1c, —OS(O)R1a, —OS(O)2R1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)NR1bR1c, —NR1aC(NR1d)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
RB is C3-10 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
each RX is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
L is C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, or heterocyclylene;
and
each R1a, R1b, R1c, and R1d is independently hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or R1a and R1c together with the C and N atoms to which they are attached form heterocyclyl;
or R1b and R1c together with the N atom to which they are attached form heterocyclyl;
wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from:
(a) deuterium, cyano, halo, nitro, and oxo;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
and (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(O)SRa, —C(NRa)NRbRc, —C(S)Ra, —C(S)ORa, —C(S)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(O)SRa, —OC(NRa)NRbRc, —OC(S)Ra, —OC(S)ORa, —OC(S)NRbRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(O)SRd, —NRaC(NRd)NRbRc, —NRaC(S)Rd, —NRaC(S)ORd, —NRaC(S)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen or deuterium;
(ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
wherein each Qa is independently selected from:
(a) deuterium, cyano, halo, nitro, and oxo;
(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl;
and (c) —C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(O)SRe, —C(NC)NRfRg, —C(S)Re, —C(S)ORe, —C(S)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(O)SRe, —OC(NRC)NRfRg, —OC(S)Re, —OC(S)ORe, —OC(S)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NReC(O)Rh, —NReC(O)ORf, —NReC(O)NRfRg, —NReC(O)SRf, —NReC(NRh)NRfRg, —NReC(S)Rh, —NReC(S)ORf, —NReC(S)NRfRg, —NReS(O)Rh, —NReS(O)2Rh, —NReS(O)NRfRg, —NReS(O)2NRfRg, —SRe, —S(O)Re, —S(O)2Re, —S(O)NRfRg, and —S(O)2NRfRg;
wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen or deuterium;
(ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
or (iii) Rf and Rg together with the N atom to which they are attached form heterocyclyl.

43 more elements

Facts

Application

18/505,975Filed 9 Nov 2023

Priority

WO PCT/CN2021/09397515 May 2021

Published

11 Apr 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07C 62/14
Polycyclic: having a carboxyl group on a condensed ring system
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 21/00
Drugs for disorders of the muscular or neuromuscular system
A61P 35/00
Antineoplastic agents