US 12,649,712 B2Granted

Indene compounds, pharmaceutical compositions thereof, and their therapeutic applications

AssigneeNucMito Pharmaceuticals Co. Ltd.

InventorsYing Su, Xiaokun Zhang, Ziwen Chen, Qingzhen Chen, Haishan Wang, Xindao Zhang, Zhiping Zeng, Yuqi Zhou, Zhiqiang Yan

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.

Claims53

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 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;
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 —O—, —S—, —S(O)—, or —S(O)2—;
and
RB is C6-14 aryl or heteroaryl;
(ii) 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
(iii) X is —N(RX)—;
and
RB and RX together with the N atom to which they are attached form heteroaryl;
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 Ria 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 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 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 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 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(NRe)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, —NRC(S)ORf, —NReC(S)NRfRg, —NReS(O)Rh, —NRS(O)2Rh, —NRS(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.

39 more elements

A compound of:

2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]acetic acid A1;
2-[(1Z)-5-fluoro-1-{[4-(4-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A2;
2-[(1Z)-1-({2-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A3;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(4-methylphenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid A4;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]acetic acid A5;
2-[(1Z)-1-{[4-(4-bromophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A6;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(3-methylphenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid A7;
2-[(1Z)-1-{[4-(3-cyanophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A8;
(Z)-2-(5-fluoro-2-methyl-1-(4-(3-(trifluoromethyl)phenoxy)benzylidene)-1H-inden-3-yl)acetic acid A9;
2-[(1Z)-1-{[4-(4-ethylphenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A10;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A11;
2-[(1Z)-1-{[2-chloro-4-(4-methoxyphenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A12;
2-[(1Z)-5-fluoro-1-({2-methoxy-4-[4-(propan-2-yl)phenoxy]phenyl}-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A13;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(naphthalen-2-yloxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid A14;
2-[(1Z)-1-({2-chloro-4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A15;
2-[(1Z)-1-{[4-(2,4-difluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A16;
2-[(1Z)-1-{[4-(2-bromo-4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A17;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(2,4,5-trifluorophenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid A18;
3-[(1Z)-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]propanoic acid A19;
2-[(1Z)-5-fluoro-1-({4-[(6-fluoropyridin-3-yl)oxy]phenyl}methylidene)-2-methyl-1H-inden-3-yl]acetic acid A20;
2-[(1Z)-5-fluoro-1-({4-[(6-fluoro-5-methylpyridin-3-yl)oxy]phenyl}-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A21;
(Z)-2-(5-fluoro-2-methyl-1-(4-(quinolin-5-yloxy)benzylidene)-1H-inden-3-yl)acetic acid A22;
2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]-N-hydroxyacetamide A23;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A24;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetamide A25;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-methylacetamid A26;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-(2-hydroxyethyl)acetamide A27;
(Z)-2-(5-fluoro-2-methyl-1-(4-phenoxybenzylidene)-1H-inden-3-yl)-N-(1H-tetrazol-5-yl)acetamide A28;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[methyl(phenyl)amino]phenyl}methylidene)-1H-inden-3-yl]acetic acid A29;
2-[(1Z)-1-({4-[benzyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A30;
2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(methyl)amino]phenyl}methylidene)-2-methyl-1H-inden-3-yl]acetic acid A31;
2-[(1Z)-1-({4-[ethyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A32;
2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(propyl)amino]phenyl}methylidene)-2-methyl-1H-inden-3-yl]acetic acid A33;
(Z)-2-(5-fluoro-1-(4-((4-fluorophenyl)(2-hydroxyethyl)amino)benzylidene)-2-methyl-1H-inden-3-yl)acetic acid A34;
2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(4-formylphenyl)amino]phenyl}-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A35;
2-[(1Z)-5-fluoro-1-({4-[(4-formylphenyl)(phenyl)amino]phenyl}methylidene)-2-methyl-1H-inden-3-yl]acetic acid A36;
2-[(1Z)-5-fluoro-2-methyl-1-({4-[methyl(phenyl)amino]phenyl}methylidene)-1H-inden-3-yl]-N-hydroxyacetamide A37;
2-[(1Z)-1-({4-[benzyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluoro-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A38;
5-{[(1Z)-2-methyl-1-[(3-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2,3,4-tetrazole A39;
5-{[(1Z)-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2,3,4-tetrazole A40;
5-{2-[(1Z)-2-methyl-1-{[4-(4-methylphenoxy)phenyl]methylidene}-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A41;
5-{2-[(1Z)-1-{[4-(4-bromophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A42;
5-{2-[(1Z)-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A43;
5-{2-[(1Z)-1-{[4-(4-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A44;
5-{2-[(1Z)-2-methyl-1-({4-[4-(trifluoromethyl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A45;
5-{2-[(1Z)-2-methyl-1-{[4-(3-methylphenoxy)phenyl]methylidene}-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A46;
3-(4-{[(1Z)-2-methyl-3-[2-(1H-1,2,3,4-tetrazol-5-yl)ethyl]-1H-inden-1-ylidene]methyl}phenoxy)benzonitrile A47;
5-{2-[(1Z)-1-{[4-(3-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A48;
5-{2-[(1Z)-1-{[4-(3-bromophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A49;
5-{2-[(1Z)-2-methyl-1-({4-[3-(trifluoromethyl)phenoxy]phenyl}methylidene)-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A50;
5-{2-[(1Z)-2-methyl-1-{[4-(naphthalen-2-yloxy)phenyl]methylidene}-1H-inden-3-yl]ethyl}-1H-1,2,3,4-tetrazole A51;
(Z)-3-((2-methyl-1-(4-phenoxybenzylidene)-1H-inden-3-yl)methyl)-1,2,4-oxadiazol-5(4H)-one A52;
5-{[(1E)-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2,3,4-tetrazole A53;
5-{[(1E)-1-[(3-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2,3,4-tetrazole A54;
2-[(1Z)-5-fluoro-2-methyl--{[4-(morpholin-4-yl)phenyl]methylidene}-1H-inden-3-yl]acetic acid A55;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(piperidin-1-yl)phenyl]methylidene}-1H-inden-3-yl]acetic acid A56;
2-[(1Z)-5-fluoro-1-{[4-(1H-indol-1-yl)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A57;
2-[(1Z)-1-{[4-(2-amino-1H-imidazol-1-yl)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]acetic acid A58;
2-[(1Z)-5-fluoro-2-methyl--{[4-(pyrrolidin-1-yl)phenyl]methylidene}-1H-inden-3-yl]acetic acid A59;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(1H-pyrrol-1-yl)phenyl]methylidene}-1H-inden-3-yl]acetic acid A60;
(2E)-3-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]prop-2-enoic acid A61;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfonyl)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A62;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfinyl)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A63;
2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)sulfanyl]phenyl}methylidene)-2-methyl-1H-inden-3-yl]acetic acid A64;
2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)pyridine-3-yl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A65;
2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)-5-methylpyridin-3-yl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A66;
(2E)-4-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]but-2-enoic acid A67;
2-[(1Z)-4,5-difluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]acetic acid A68;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2,4-dimethyl-1H-inden-3-yl]acetic acid A69;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(morpholin-4-yl)phenyl]methylidene}-1H-inden-3-yl]-N-hydroxyacetamide A70;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(piperidin-1-yl)phenyl]methylidene}-1H-inden-3-yl]-N-hydroxyacetamide A71;
2-[(1Z)-5-fluoro-1-{[4-(1H-indol-1-yl)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A72;
2-[(1Z)-1-{[4-(2-amino-1H-imidazol-1-yl)phenyl]methylidene}-5-fluoro-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A73;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(pyrrolidin-1-yl)phenyl]methylidene}-1H-inden-3-yl]-N-hydroxyacetamide A74;
2-[(1Z)-5-fluoro-2-methyl-1-{[4-(1H-pyrrol-1-yl)phenyl]methylidene}-1H-inden-3-yl]-N-hydroxyacetamide A75;
(2E)-3-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyprop-2-enamide A76;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfonyl)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A77;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfinyl)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A78;
2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)sulfanyl]phenyl}methylidene)-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A79;
2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)pyridine-3-yl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A80;
2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)-5-methylpyridin-3-yl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A81;
(2E)-4-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxybut-2-enamide A82;
2-[(1Z)-4,5-difluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A83;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2,4-dimethyl-1H-inden-3-yl]-N-hydroxyacetamide A84;
or
2-[(1Z)-5-Fluoro-1-({4-[(4-fluorophenyl)(2-hydroxyethyl)amino]phenyl}-methylidene)-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A85;
2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]-N-hydroxy-N-methylacetamide C1;
2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-inden-3-yl]-N-hydroxy-N-methylacetamide C2;
(Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)-N-hydroxy-N-methylacetamide C3;
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;
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;
and
2-[(1E)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]-acetic acid E6;
or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

133 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/001,309Filed 11 Jun 2021 · us provisional application
Priority: 12 Jun 2020
Published: US 2023/0234909 A127 Jul 2023
Granted: 9 Jun 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification36 codes

C07C 59/135
Saturated compounds having only one carboxyl group and containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE…
C07C 59/68
The non-carboxylic part of the ether containing six-membered aromatic rings: the oxygen atom of the ether group being bound to a non-condensed…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism

Family

Application63/038,737Us provisional application · filed 12 Jun 2020
US 2023/0234909 A1Pre-grant publication · published 27 Jul 2023
US 12,649,712 B2This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

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 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;
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 —O—, —S—, —S(O)—, or —S(O)2—;
and
RB is C6-14 aryl or heteroaryl;
(ii) 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
(iii) X is —N(RX)—;
and
RB and RX together with the N atom to which they are attached form heteroaryl;
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 Ria 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 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 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 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 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(NRe)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, —NRC(S)ORf, —NReC(S)NRfRg, —NReS(O)Rh, —NRS(O)2Rh, —NRS(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.

39 more elements

Facts

Application

18/001,309Filed 11 Jun 2021 · us provisional application

Priority

12 Jun 2020

Published

US 2023/0234909 A127 Jul 2023

Granted

9 Jun 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification36 codes

C07C 59/135
Saturated compounds having only one carboxyl group and containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE…
C07C 59/68
The non-carboxylic part of the ether containing six-membered aromatic rings: the oxygen atom of the ether group being bound to a non-condensed…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism