| Literature DB >> 28185720 |
Cheng Zhu1, Liping Wang2, Yuping Zhu3, Zack Zhiqiang Guo2, Ping Liu3, Zhiyong Hu3, Jason W Szewczyk2, Ling Kang2, Gary Chicchi2, Anka Ehrhardt2, Andrea Woods2, Toru Seo2, Morgan Woods3, Margaret van Heek3, Karen H Dingley3, Jianmei Pang3, Gino M Salituro2, Joyce Powell2, Jenna L Terebetski3, Viktor Hornak2, Louis-Charles Campeau2, Robert K Orr2, Feroze Ujjainwalla3, Michael Miller3, Andrew Stamford2, Harold B Wood3, Timothy Kowalski3, Ravi P Nargund3, Scott D Edmondson3.
Abstract
The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physicochemical properties. Pharmacokinetic data of compound 17 in rat, dog and rhesus will be described. Compound 17 was suitable for QD dosing based on its predicted human half-life, and its projected human dose was much lower than that of the recently reported structurally-related benzyloxy compound 2. Compound 17 was selected as a tool compound candidate for NHP (Non-Human Primate) efficacy studies.Entities:
Keywords: Cis cyclopropane; GPR119 agonist; Glucose dependent insulin secretion; Phenyl acetamide; Type 2 diabetes
Mesh：
Substances：
Year: 2017 PMID： 28185720 DOI： 10.1016/j.bmcl.2017.01.091
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823