Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1378871 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
Abstract
The optimisation of a series of glucokinase activators is described, including attempts to uncouple the relationship between potency and plasma protein binding, and to better understand the key pharmacokinetic properties of the series. The use of unbound clearance as an optimisation parameter facilitated the identification of GKA50, a compound which combines excellent potency and pharmacokinetics with good free drug levels and solubility, and exhibits in vivo efficacy at 1 mg/kg po in an acute rat OGTT model.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Darren McKerrecher, Joanne V. Allen, Peter W.R. Caulkett, Craig S. Donald, Mark L. Fenwick, Emma Grange, Keith M. Johnson, Craig Johnstone, Clifford D. Jones, Kurt G. Pike, John W. Rayner, Rolf P. Walker,