SAR, Pharmacokinetics, Safety, and Efficacy of Glucokinase Activating 2-(4-Sulfonylphenyl)-N-thiazol-2-ylacetamides: Discovery of PSN-GK1.
作者
Bertram, Lisa S.;Black, Daniel;Briner, Paul H.;Chatfield, Rosemary;Cooke, Andrew;Fyfe, Matthew C. T.;Murray, P. John;Naud, Frederic;Nawano, Masao;Procter, Martin J.;Rakipovski, Gunaj;Rasamison, Chrystelle M.;Reynet, Christine;Schofield, Karen L.;Shah, Vil
[摘要]：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 (I, PSN-GK1), a potent GK activator with an improved pharmacokinetic and safety profile, is described. Following oral administration, this compd. elicited robust glucose lowering in rats.
