Pharmaceutical composition for treating fatty liver disease

Inventors

Yukioka, Hideo • SHIMAZAKI, Atsuyuki • Hamada, Tadateru • Ohyabu, Naoki

Assignees

Shionogi and Co Ltd

Abstract

Provided is a pharmaceutical composition for treating and/or preventing fatty liver disease, particularly nonalcoholic fatty liver disease, the pharmaceutical composition having an excellent ACC2-selective inhibitory action and having no side effects such as an increase in plasma triglyceride or a decrease in platelet concentration.A pharmaceutical composition for treating and/or preventing fatty liver disease, the pharmaceutical composition comprising a compound represented by Formula (I):whereinR1 is haloalkyl or non-aromatic carbocyclyl,R2 is a hydrogen atom or halogen,R3 is halogen,ring A is a group represented by the formula:-L1- is —O—(CH2)—, —(CH2)2—, or the like,R4 is alkyl or haloalkyl, andR5 is alkylcarbonyl or carbamoyl,or a pharmaceutically acceptable salt thereof.

Core Innovation

The invention relates to pharmaceutical compositions and treatment methods using a compound represented by Formula (I), including pharmaceutically acceptable salts, as an ACC2 inhibitor for fatty liver disease. The treated condition is nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), including progression to NASH fibrosis, liver cirrhosis, and NASH-associated hepatocellular carcinoma (HCC). The described approach is directed to individuals in need of treating the fatty liver disease by administering an effective amount of the Formula (I) compound or pharmaceutically acceptable salt.

The method coverage is further refined by specifying Formula (I) selections and by targeting particular fatty-liver disease subtypes and complications. Dependent claim refinements identify NAFLD, liver fibrosis caused by NASH, liver cirrhosis caused by NASH, and hepatocellular carcinoma caused by NASH as the fatty liver disease to be treated. Additional dependent features describe outcome characterization, including improved insulin resistance and assertions regarding lack of certain side effects.

The disclosed framework also includes combination therapy for treating fatty liver disease. A method is described in which a compound represented by Formula (I) or a pharmaceutically acceptable salt is administered together with at least one compound selected from obeticholic acid, semaglutide, and resmetirom or pharmaceutically acceptable salts. The document states that combination therapy is more effective than monotherapy, and the described safety and efficacy features include no increase in plasma triglycerides, low cardiovascular risk, no platelet concentration decrease, and improved insulin resistance.

Claims Coverage

The document includes two independent methods. One independent claim covers administering an effective amount of a Formula (I) compound or pharmaceutically acceptable salt for fatty liver disease, and the second independent claim covers administering a combination that includes a Formula (I) compound plus at least one selected from obeticholic acid, semaglutide, and resmetirom. Across the independent claims, the inventive focus centers on two inventive features.

Across the independent claims, treatment of fatty liver disease is provided by administering a Formula (I) compound alone or in combination with at least one of obeticholic acid, semaglutide, and resmetirom, with dependent refinements directed to NAFLD/NASH subtypes and NASH-associated fibrosis, cirrhosis, and hepatocellular carcinoma.

Stated Advantages

Documented Applications