Novel 5-nitropyrimidine derivatives bearing endo-azabicyclic alcohols/amines as potent GPR119 agonists

详细信息    查看全文

• 关键词：GPR119 agonists ; 5-Nitropyrimidine ; endo-Azabicyclic alcohol ; Full agonists
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：254-260
• 全文大小：1531 K
• 卷排序：25

文摘

A series of GPR119 agonists based on a 5-nitropyrimidine scaffold bearing endo-azabicyclic substituents were synthesized and evaluated for their GPR119 agonistic activities. Most compounds exhibited much stronger EC50 values than that of oleoylethanolamide (OEA). Among them, derivatives from endo-azabicyclic alcohols displayed more potent GPR119 agonistic activities than compounds with endo-azabicyclic amines. Especially the optimized compounds (6, 7, 8, 12, 17) were shown to have potent biological activities and were identified as full agonists. Isopropyl carbamate compound 8 synthesized from endo-azabicyclic alcohol was observed to have the best EC50 value (0.6 nM). Generally 2-fluoro substitution of the aryl group at the C4 position of 5-nitropyrimidine scaffold resulted in the increase of biological activity.