Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372623 | Bioorganic & Medicinal Chemistry Letters | 2009 | 6 Pages |
Abstract
A promising area of novel anti-diabetic therapy involves identification of small molecule activators of the glucokinase enzyme to reduce blood glucose and normalize glucose stimulated insulin secretion. Herein, we report the identification and optimization of a series of 4-sulfonyl-2-pyridone activators. The activators were evaluated for in vitro biochemical activation and pharmacokinetic properties. As part of these efforts, a unique metabolic liability of the 4-sulfonyl-2-pyridone ring system was identified wherein this heterocycle readily undergoes conjugation with glutathione under non-enzymatic conditions.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jeffrey A. Pfefferkorn, Jihong Lou, Martha L. Minich, Kevin J. Filipski, Mingying He, Ru Zhou, Syed Ahmed, John Benbow, Angel-Guzman Perez, Meihua Tu, John Litchfield, Raman Sharma, Karen Metzler, Francis Bourbonais, Cong Huang, David A. Beebe,