Thiazolidinedione analogs for the treatment of NAFLD and metabolic diseases

Inventors

Colca, Gerard R.

Assignees

Cirius Therapeutics Inc

Abstract

Provided herein are thiazolidinedione analogues that are useful for treating non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), diabetes, and other metabolic inflammation-mediated disease and disorders.

Core Innovation

The document describes compounds of structural Formula (I), including pharmaceutically acceptable salts, as mitochondrial pyruvate carrier (MPC) modulators and thiazolidinedione analogs. The compounds include pharmaceutically acceptable salts, including potassium salt forms and deuterium variants, with variable substitutions such as phenyl, alkoxy, and halo variants and deuterium at a specified position (R3). The invention further provides pharmaceutical compositions comprising the compound or a pharmaceutically acceptable salt and a pharmaceutically acceptable excipient.

The compounds are administered for treating non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), diabetes mellitus, metabolic syndrome, and metabolic inflammation-mediated diseases. The therapeutic concept includes modulating MPC activity and reducing PPARγ binding/activation, with an objective of improving glucose tolerance and insulin sensitivity, treating or preventing hepatic diseases, and preventing hepatocyte fibrogenesis.

The document further describes combination treatment and co-administration concepts, including administering a GLP1 agonist together with the compound. The GLP1 agonist embodiments include exenatide, liraglutide, semaglutide, and dulaglutide, and the combination is framed for use in subject treatment regimens.

Claims Coverage

The independent claims cover combination therapy using a structural Formula (I) compound or pharmaceutically acceptable salt together with a GLP1 agonist for treating NAFLD, NASH, diabetes mellitus, and/or metabolic syndrome. Across the independent claims, the inventive features center on three claim families, each distinguished by dosing, salt form, route, or composition format.

Across the independent claims, the protected subject matter is directed to combination therapy using a structural Formula (I) compound, including pharmaceutically acceptable salt forms such as potassium salt, administered in a specified daily dosage range together with a GLP1 agonist. Claim distinctions are based on salt form, oral administration, and pharmaceutical composition formatting with a pharmaceutically acceptable excipient.

Stated Advantages

Documented Applications