Title of article
Design of a potent, soluble glucokinase activator with excellent in vivo efficacy
Author/Authors
Darren McKerrecher، نويسنده , , Joanne V. Allen، نويسنده , , Peter W.R. Caulkett، نويسنده , , Craig S. Donald، نويسنده , , Mark L. Fenwick، نويسنده , , Emma Grange، نويسنده , , Keith M. Johnson، نويسنده , , Craig Johnstone، نويسنده , , Clifford D. Jones، نويسنده , , Kurt G. Pike، نويسنده , , John W. Rayner، نويسنده , , Rolf P. Walker، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2006
Pages
5
From page
2705
To page
2709
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.
Keywords
Kinase activator , Unbound clearance , Glucokinase , GKA50 , diabetes
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2006
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
796852
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