Document Report Card

ID: ALA1821692

Journal: J Med Chem

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

Authors: Kamisuki S, Shirakawa T, Kugimiya A, Abu-Elheiga L, Choo HY, Yamada K, Shimogawa H, Wakil SJ, Uesugi M.

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.

CiteXplore: 21561152

DOI: 10.1021/jm200304y