| Literature DB >> 18588279 |
Lisa S Bertram1, Daniel Black, Paul H Briner, Rosemary Chatfield, Andrew Cooke, Matthew C T Fyfe, P John Murray, Frédéric Naud, Masao Nawano, Martin J Procter, Günaj Rakipovski, Chrystelle M Rasamison, Christine Reynet, Karen L Schofield, Vilas K Shah, Felix Spindler, Amanda Taylor, Roy Turton, Geoffrey M Williams, Philippe Wong-Kai-In, Kosuke Yasuda.
Abstract
Allosteric activators of the glucose-sensing enzyme glucokinase (GK) are currently attracting much interest as potential antidiabetic therapies because they can achieve powerful blood glucose lowering through actions in multiple organs. Here, the optimization of a weakly active high-throughput screening hit to (2 R)-2-(4-cyclopropanesulfonylphenyl)- N-(5-fluorothiazol-2-yl)-3-(tetrahydropyran-4-yl)propionamide (PSN-GK1), a potent GK activator with an improved pharmacokinetic and safety profile, is described. Following oral administration, this compound elicited robust glucose lowering in rats.Entities:
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Year: 2008 PMID： 18588279 DOI： 10.1021/jm8003202
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446