Synthesis and evaluation of diarylthiazole derivatives that inhibit activation of sterol regulatory element-binding proteins.

ABSTRACT: Fatostatin, a recently discovered small molecule that inhibits activation of sterol regulatory element-binding protein (SREBP), blocks biosynthesis and accumulation of fat in obese mice. We synthesized and evaluated a series of fatostatin derivatives. Our structure-activity relationships led to the identification of N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide (24, FGH10019) as the most potent druglike molecule among the analogues tested. Compound 24 has high aqueous solubility and membrane permeability and may serve as a seed molecule for further development.

SUBMITTER: Kamisuki S 

PROVIDER: S-EPMC3136361 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature