Discovery of 2-Pyridylureas as Glucokinase Activators
| Autor: | Kevin Ronald Condroski, Susan P. Rhodes, Maralee McVean, Walter C. Voegtli, Christopher F. Kraser, Walter E. DeWolf, Lance A. Williams, Deborah Anderson, Hillary L. Sturgis, Boyd Steven A, Ronald Jay Hinklin, Jonathan B. Houze, Brian R. Baer, Thomas Daniel Aicher |
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| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Pyridines Glucokinase Chemistry Insulin medicine.medical_treatment Enzyme Activators Diabetic mouse Type 2 diabetes Glucose Tolerance Test medicine.disease Mice Inbred C57BL medicine.anatomical_structure Endocrinology Internal medicine Drug Discovery medicine Animals Urea Molecular Medicine Transferase Oral glucose tolerance Pancreas Flux (metabolism) |
| Zdroj: | Journal of Medicinal Chemistry. 57:8180-8186 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Glucokinase (GK) is the rate-limiting step for insulin release from the pancreas in response to high levels of glucose. Flux through GK also contributes to reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can allosterically activate GK may address this issue. Herein we report the identification and initial optimization of a novel series of glucokinase activators (GKAs). Optimization led to the identification of 33 as a compound that displayed activity in an oral glucose tolerance test (OGTT) in normal and diabetic mice. |
| Databáze: | OpenAIRE |
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