1432500-06-5Relevant articles and documents
The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus
Guzman-Perez, Angel,Pfefferkorn, Jeffrey A.,Lee, Esther C.Y.,Stevens, Benjamin D.,Aspnes, Gary E.,Bian, Jianwei,Didiuk, Mary T.,Filipski, Kevin J.,Moore, Dianna,Perreault, Christian,Sammons, Matthew F.,Tu, Meihua,Brown, Janice,Atkinson, Karen,Litchfield, John,Tan, Beijing,Samas, Brian,Zavadoski, William J.,Salatto, Christopher T.,Treadway, Judith
, p. 3051 - 3058 (2013/06/27)
A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5- dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido] propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation.
