Design of a potent, soluble glucokinase activator with excellent in vivo efficacy
| Autor: | Craig Johnstone, Rolf Peter Walker, Emma Grange, Peter William Rodney Caulkett, Kurt Gordon Pike, Rayner John Wall, Craig S. Donald, Darren Mckerrecher, Mark L. Fenwick, Keith M. Johnson, Joanne V. Allen, Clifford David Jones |
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| Rok vydání: | 2006 |
| Předmět: |
Glucokinase
medicine.drug_class Chemistry Binding protein Organic Chemistry Clinical Biochemistry Pharmaceutical Science Enzyme Activators Carboxamide Biological activity Plasma protein binding Biochemistry Pharmacokinetics In vivo Drug Design Drug Discovery medicine Molecular Medicine Potency Molecular Biology |
| Zdroj: | Bioorganicmedicinal chemistry letters. 16(10) |
| ISSN: | 0960-894X |
| Popis: | 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 1mg/kg po in an acute rat OGTT model. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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