Prevention and treatment of non-alcoholic fatty liver disease

A method for treating or reducing the risk of developing non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof, the method comprising administering a composition comprising a therapeutically effective amount of one or more methimazole derivatives to the subject, wherein the one or more methimazole derivatives have a formula selected from (X) and (XI):

• or pharmaceutically-acceptable salts or solvates thereof;
• wherein:
• (a) Y is selected from H, C1-C4 alkyl, C1-C4 and substituted alkyl;
• (b) R1 is selected from H, OH, halogens, C1-C4 alkyl, C1-C4 substituted alkyl, C1-C4 ester, and C1-C4 substituted ester;
• (c) R2 is independently selected from H, C1-C4 alkyl, and C1-C4 substituted alkyl;
• (d) R4 is selected from H, C1-C4 alkyl, and C1-C4 substituted alkyl;
• (e) Z is selected from SR3 and OR3;
• wherein R3 is selected from H, C1-C4 alkyl, C1-C4 substituted alkyl, and —CH2Ph,
• wherein Ph is phenyl;
• (f) X is selected from S and O.

A pharmaceutical composition for treatment of or reduction of the risk of developing non-alcoholic fatty liver disease (NAFLD) comprising:

• (a) a therapeutically effective amount of one or more of metformin, thiazolidinediones, or HMG-Co-A inhibitors;
• and
• (b) a therapeutically effective amount of one or more methimazole derivatives having a formula selected from (I), (II), and (III):
• or pharmaceutically-acceptable salts or solvates thereof;
• wherein:
• (i) Y is independently selected from H, C1-C4 alkyl, C1-C4 substituted alkyl, NO2, and a phenyl moiety having Formula (IV):
• wherein no more than one Y of a methimazole derivative may be the phenyl moiety of Formula (IV);
• R1 is selected from H, OH, halogens, C1-C4 alkyl, C1-C4 substituted alkyl, C1-C4 ester, and C1-C4 substituted ester;
• and R4 is selected from H, C1-C4 alkyl, and C1-C4 substituted alkyl;
• (ii) R2 is independently selected from H, C1-C4 alkyl, and C1-C4 substituted alkyl;
• (iii) Z is selected from SR3, S(O)R3, OR3, and C1-C4 alkyl;
• wherein R3 is selected from H, C1-C4 alkyl, C1-C4 substituted alkyl, and —CH2Ph,
• wherein Ph is phenyl;
• and
• (iv) X is selected from S and O.