期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 5, 期 10, 页码 1114-1118出版社
AMER CHEMICAL SOC
DOI: 10.1021/ml500240d
关键词
sGPR39 agonists; GPR39 receptor; Zn2+-sensing receptor; antidiabetic treatment; fl-cell protection; GLP-I secretion; insulin secretion
The identification of highly potent and orally bioavailable GPR39 agonists is reported. Compound 1, found in a phenotypic screening campaign, was transformed into compound 2 with good activity on both the rat and human GPR39 receptor. This compound was further optimized to improve ligand efficiency and pharmacokinetic properties to yield GPR39 agonists for the potential oral treatment of type 2 diabetes. Thus, compound 3 is the first potent GPR39 agonist (EC(50)s <= 1 nM for human and rat receptor) that is orally bioavailable in mice and robustly induced acute GLP-1 levels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据