936246-98-9Relevant academic research and scientific papers
Identification of a new class of glucokinase activators through structure-based design
Hinklin, Ronald J.,Boyd, Steven A.,Chicarelli, Mark J.,Condroski, Kevin R.,Dewolf, Walter E.,Lee, Patrice A.,Lee, Waiman,Singh, Ajay,Thomas, Laurie,Voegtli, Walter C.,Williams, Lance,Aicher, Thomas D.
, p. 7669 - 7678 (2013)
Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high glucose concentrations. Glucose flux through GK also contributes to reducing hepatic glucose output. Because many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, compounds that can activate GK may serve as effective treatments for type 2 diabetes. Herein we report the identification and initial optimization of a novel series of allosteric glucokinase activators (GKAs). We discovered an initial thiazolylamino pyridine-based hit that was optimized using a structure-based design strategy and identified 26 as an early lead. Compound 26 demonstrated a good balance of in vitro potency and enzyme kinetic parameters and demonstrated blood glucose reductions in oral glucose tolerance tests in both C57BL/6J mice and high-fat fed Zucker diabetic fatty rats.
GLUCOKINASE ACTIVATORS
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Page/Page column 78-79, (2010/11/27)
Provided are compounds of Formula I wherein R1, R2, Y, Z and G are as defined herein, that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.
