Design, synthesis and SAR of novel glucokinase activators

作者：Cheruvallath Zacharia S^*; Gwaltney Stephen L II; Sabat Mark; Tang Mingnam; Feng Jun; Wang Haixia; Miura Joanne; Guntupalli Prasuna; Jennings Andy; Hosfield David; Lee Bumsup; Wu Yiqin

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(7): 2166-2171.

DOI：10.1016/j.bmcl.2013.01.093

• Glucokinase activator
• Structure-based drug design
• OGTT
• Type 2 diabetes
• 6-Methyl pyridone

Guided by co-crystal structures of compounds 15, 22 and 30, an SBDD approach led to the discovery of the 6-methyl pyridone series as a novel class of GKAs that potently activate GK in enzyme and cell assays. Anti-diabetic OGTT efficacy was demonstrated with 54 in a mouse model of type 2 diabetes.

• 出版日期2013-4-1