Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists
Year: 2014
Type: article
Abstract: We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml4005123
Authors: Xiaohui Du, Paul J. Dransfield, Daniel C.-H. Lin, Simon Wong, Yingcai Wang, Zhongyu Wang, Todd Kohn, Ming Yu, Sean P. Brown, Marc Vimolratana, Liusheng Zhu, An-Rong Li, Yongli Su, Xianyun Jiao, Jiwen (Jim) Liu, Gayathri Swaminath, Thanhvien Tran, Jian Luo, Run Zhuang, Jane Zhang, Qi Guo, Frank Li, Richard Connors, Julio C. Medina, Jonathan B. Houze
Institution: Amgen (United States)
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1974530518