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US 2023/0147993 A1Published application
Thiophene compounds with cyclic amides, and uses thereof
AssigneeCapulus Therapeutics, LLC
InventorsMichael John GREEN, Barry Patrick HART
Life of this patent
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Abstract
Provided herein are compounds comprising a four-ring core, such as compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, tautomers, isotopes, or isomers thereof. Also provided herein are methods of inhibiting a component of the sterol regulatory element binding protein (SREBP) pathway, such as an SREBP or SREBP cleavage activating protein (SCAP), using these compounds, or pharmaceutically acceptable salts, solvates, tautomers, isotopes, or isomers thereof. Further provided are methods of treating a disorder in a subject in need thereof, such as liver disease, non-alcoholic steatohepatitis, insulin resistance, or cancer.
Claims43
A compound of Formula (II):
- or a pharmaceutically acceptable salt, solvate, tautomer, isotope, or isomer thereof, wherein:
- ring I is 3- to 10-membered heterocycloalkyl;
- m is an integer from 0 to 8;
- each R1 is independently halo, oxo, alkyl, or —OR4, wherein each alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- n is 0, 1 or 2;
- each R2 is independently halo, alkyl, or haloalkyl;
- R3a is:
- (C3-C10)cycloalkyl substituted with one or more substituents independently selected from the group consisting of halo and —OR5;
- (C3-C10)cycloalkyl substituted with one or more alkyl, wherein the cycloalkyl and each alkyl are independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OR6;
- heterocycloalkyl connected through an annular carbon, wherein the heterocycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, alkyl, and —OR7, wherein each alkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- —OR9, wherein R9 is heterocycloalkyl, (C3-C10)cycloalkyl, or alkyl, wherein the alkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of —OH, halo, heterocycloalkyl, and (C3-C10)cycloalkyl, and wherein each heterocycloalkyl and cycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of alkyl, halo, and —OH;
- —CH2—(C3-C10)cycloalkyl substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- or
- R3b is hydrogen, or together with R3a and the atoms to which they are attached forms a non-aromatic heterocyclyl group, wherein the non-aromatic heterocyclyl group is unsubstituted or substituted with one or more substituents independently selected from the group of halo and alkyl;
- wherein each alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group of halo and —OH;
- each R4, R5, R6, and R7 is independently hydrogen, alkyl, haloalkyl, or —C(O)CHR8—NH2, wherein R8 is a (C1-C6)alkyl.
13 more elements
A compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate, tautomer, isotope, or isomer thereof, wherein:
- ring I is 3- to 10-membered heterocycloalkyl;
- m is an integer from 0 to 8;
- each R1 is independently halo, oxo, alkyl, or —OR4, wherein each alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- n is 0, 1 or 2;
- each R2 is independently halo, alkyl, or haloalkyl;
- R3a is:
- (C3-C10)cycloalkyl substituted with one or more substituents independently selected from the group consisting of halo and —OR5;
- (C3-C10)cycloalkyl substituted with one or more alkyl, wherein the cycloalkyl and each alkyl are independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OR6;
- heterocycloalkyl connected through an annular carbon, wherein the heterocycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, alkyl, and —OR7, wherein each alkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- —OR9, wherein R9 is heterocycloalkyl, (C3-C10)cycloalkyl, or alkyl, wherein the alkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of —OH, halo, and (C3-10)cycloalkyl, and wherein each heterocycloalkyl and cycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- —CH2—(C3-C10)cycloalkyl substituted with one or more substituents independently selected from the group consisting of halo and —OH;
- or
- R3b is hydrogen, or together with R3a and the atoms to which they are attached forms a non-aromatic heterocyclyl group, wherein the non-aromatic heterocyclyl group is unsubstituted or substituted with one or more substituents independently selected from the group of halo and alkyl;
- wherein each alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group of halo and —OH;
- each R4, R5, R6, and R7 is independently hydrogen, alkyl, haloalkyl, or —C(O)CHR8—NH2, wherein R8 is a (C1-C6)alkyl.
13 more elements
-50. (canceled)
Dependencies are inferred from the claim text.