Discovery of LY3325656: A GPR142 agonist suitable for clinical testing in human. Issue 5 (1st March 2020)

• Record Type: Journal Article
• Authors: Liu, Lian Zhu; Ma, Tianwei; Zhou, Jingye; Long Hu, Zhi; Jun Zhang, Xue; Zhen Zhang, Hai; Zeng, Mi; Liu, Jia; Li, Lei; Jiang, Yi; Zou, Zack; Wang, Fan; Zhang, Lei; Xu, Jianfeng; Wang, Jingru; Xiao, Fei; Fang, Xiankang; Zou, Haixia; Efanov, Alexander M.; Thomas, Melissa K; Lin, Hua V.; Chen, Jiehao
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 5(2020)
• Publication Date: 2020-03-01
• Subjects: Type 2 diabetes -- Glucose-dependent insulin secretion -- GPR142 agonist -- Metabolism; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.126857
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The discovery and optimization of a novel series of GPR142 agonists are described. These led to the identification of compound 21 (LY3325656), which demonstrated anti-diabetic benefits in pre-clinical studies and ADME/PK properties suitable for human dosing. Compound 21 is the first GPR142 agonist molecule advancing to phase 1 clinic trials for the treatment of Type 2 diabetes.