Discovery of new nanomolar inhibitors of GPa: Extension of 2-oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors

详细信息    查看全文

• 作者：Wendy A. Loughlin^a ; ^{w.loughlin@griffith.edu.au} ; Ian D. Jenkins^b ; N. David Karis^b ; Peter C. Healy^a ; ^c
• 关键词：Glycogen phosphorylase inhibitors ; Pyridone amides ; Dimer ; Structure activity relationship ; Type 2 diabetes
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：127
• 期：Complete
• 页码：341-356
• 全文大小：1748 K
• 卷排序：127

文摘

Design and synthesis of 14 new pyridone amide inhibitors of Glycogen Phosphorylase. Third generation library hit rate was 36%, with 5 compounds inhibiting GPa with an IC50 value. Dimers 39 and 43 were identified as new nanomolar inhibitors of GPa (IC50 = 230 and 260 nM). SAR analysis revealed sensitivity of GPa to substitution of the pyridone ring. SAR analysis revealed some sensitivity of GPa to the presence of the amide group.