Pharmaceutical composition for treating fatty liver disease
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): wherein R 1 is haloalkyl or non-aromatic carbocyclyl, R 2 is a hydrogen atom or halogen, R 3 is halogen, ring A is a group represented by the formula: -L 1 - is —O—(CH 2 )—, —(CH 2 ) 2 —, or the like, R 4 is alkyl or haloalkyl, and R 5 is alkylcarbonyl or carbamoyl, or a pharmaceutically acceptable salt thereof.
1 . A method of treating a fatty liver disease, the method comprising:
a step of administering an effective amount of a compound represented by Formula (I):
wherein
R 1 is haloalkyl or non-aromatic carbocyclyl,
R 2 is a hydrogen atom or halogen,
R 3 is halogen,
ring A is a group represented by the formula:
-L 1 - is —O—(CH 2 )—, —(CH 2 ) 2 —, —(CH 2 )—(CF 2 )—, or —(CF 2 )—(CH 2 )— (wherein a left bond is attached to the ring A and a right bond is attached to a group represented by the formula:
R 4 is alkyl or haloalkyl, and
R 5 is alkylcarbonyl or carbamoyl,
or a pharmaceutically acceptable salt thereof,
to an individual in need of treating the fatty liver disease.
2 . The method according to claim 1 , wherein the compound represented by Formula (I) is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
3 . The method according to claim 1 , wherein the fatty liver disease is nonalcoholic fatty liver disease (NAFLD).
4 . The method according to claim 1 , wherein the fatty liver disease is nonalcoholic steatohepatitis (NASH).
5 . The method according to claim 1 , wherein the fatty liver disease is liver fibrosis caused by NASH.
6 . The method according to claim 1 , wherein the fatty liver disease is liver cirrhosis caused by NASH.
7 . The method according to claim 1 , wherein the fatty liver disease is hepatocellular carcinoma (HCC) caused by NASH.
8 . The method according to claim 1 , which has no side effects of an increase in plasma triglyceride by administration of the compound represented by Formula (I) or the pharmaceutically acceptable salt thereof.
9 . The method according to claim 1 , which has no side effects of cardiovascular disease by administration of the compound represented by Formula (I) or the pharmaceutically acceptable salt thereof.
10 . The method according to claim 1 , wherein insulin resistance is improved by administration of the compound represented by Formula (I) or the pharmaceutically acceptable salt thereof.
11 . The method according to claim 1 , which has no side effects of a decrease in platelet concentration by administration of the compound represented by Formula (I) or the pharmaceutically acceptable salt thereof.
12 . A method of treating a fatty liver disease, the method comprising administering a combination of:
a compound represented by Formula (I):
wherein
R 1 is haloalkyl or non-aromatic carbocyclyl,
R 2 is a hydrogen atom or halogen,
R 3 is halogen,
ring A is a group represented by the formula:
-L 1 - is —O—(CH 2 )—, —(CH 2 ) 2 —, —(CH 2 )—(CF 2 )—, or —(CF 2 )—(CH 2 )— (wherein a left bond is attached to the ring A and a right bond is attached to a group represented by the formula:
R 4 is alkyl or haloalkyl, and
R 5 is alkylcarbonyl or carbamoyl,
or a pharmaceutically acceptable salt thereof; and
at least one compound selected from the group consisting of obeticholic acid, semaglutide, and resmetirom, or a pharmaceutically acceptable salt thereof,
to an individual in need of treating the fatty liver disease.
13 . The method according to claim 12 , wherein the compound represented by Formula (I) is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
14 . The method according to claim 12 , wherein the fatty liver disease is nonalcoholic fatty liver disease (NAFLD).
15 . The method according to claim 12 , wherein the fatty liver disease is nonalcoholic steatohepatitis (NASH).
16 . The method according to claim 12 , wherein the fatty liver disease is liver fibrosis caused by NASH.
17 . The method according to claim 12 , wherein the fatty liver disease is liver cirrhosis caused by NASH.
18 . The method according to claim 12 , wherein the fatty liver disease is hepatocellular carcinoma (HCC) caused by NASH.