Design and preparation of N-linked hydroxypyridine-based APJ agonists
Bioorganic & Medicinal Chemistry Letters(2022)
摘要
Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage.
更多查看译文
关键词
Apelin,APJ,Heart failure,Hydroxypyridine,Small molecule
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要