SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: discovery of PSN-GK1.
J Med Chem
; 51(14): 4340-5, 2008 Jul 24.
Article
in En
| MEDLINE
| ID: mdl-18588279
ABSTRACT
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 (2 R)-2-(4-cyclopropanesulfonylphenyl)- N-(5-fluorothiazol-2-yl)-3-(tetrahydropyran-4-yl)propionamide (PSN-GK1), a potent GK activator with an improved pharmacokinetic and safety profile, is described. Following oral administration, this compound elicited robust glucose lowering in rats.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfones
/
Thiazoles
/
Glucokinase
/
Hypoglycemic Agents
Limits:
Animals
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2008
Document type:
Article
Affiliation country: