Design of a potent, soluble glucokinase activator with increased pharmacokinetic half-life
| Autor: | Darren Mckerrecher, Kurt Gordon Pike, Peter William Rodney Caulkett, Ingrid Wilson, Mark L. Fenwick, Craig S. Donald, Rolf Peter Walker, David S. Clarke, Craig Johnstone, Rayner John Wall, Keith M. Johnson, Joanne V. Allen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.drug_class
Pyridines Clinical Biochemistry Pharmaceutical Science Enzyme Activators Carboxamide Biochemistry Structure-Activity Relationship Dogs Pharmacokinetics Drug Discovery Glucokinase medicine Structure–activity relationship Animals Humans Hypoglycemic Agents Molecular Biology chemistry.chemical_classification Molecular Structure Activator (genetics) Organic Chemistry Biological activity Bioavailability Rats Enzyme Activation Enzyme chemistry Solubility Drug Design Molecular Medicine Half-Life |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(11) |
| ISSN: | 1464-3405 |
| Popis: | The continued optimization of a series of glucokinase activators is described, including attempts to understand the interplay between molecular structure and the composite parameter of unbound clearance. These studies resulted in the discovery of a new scaffold for glucokinase activators and further exploration of this scaffold led to the identification of GKA60. GKA60 maintains an excellent balance of potency and physical properties whilst possessing a significantly different, but complimentary, pre-clinical pharmacokinetic profile compared with the previously disclosed compound GKA50. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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