Synthesis and biological evaluation of thiazole derivatives as GPR119 agonists. Issue 23 (1st December 2017)

• Record Type: Journal Article
• Authors: Kim, Hyojin; Cho, Suk Joon; Yoo, Minjin; Kang, Seung Kyu; Kim, Kwang Rok; Lee, Hwan Hee; Song, Jin Sook; Rhee, Sang Dal; Jung, Won Hoon; Ahn, Jin Hee; Jung, Jae-Kyung; Jung, Kwan-Young
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 23(2017)
• Page Start: 5213
• Page End: 5220
• Publication Date: 2017-12-01
• Subjects: GPR119 agonists -- Type 2 diabetes -- 4-(Phenoxymethyl)thiazole -- Pyrrolidine-2, 5-dione -- OGTT; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.10.046
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of 4-(phenoxymethyl)thiazole derivatives was synthesized and evaluated for their GPR119 agonistic effect. Several 4-(phenoxymethyl)thiazoles with pyrrolidine-2, 5-dione moieties showed potent GPR119 agonistic activities. Among them, compound27 and32d showed good in vitro activity with an EC50 value of 49 nM and 18 nM, respectively with improved human and rat liver microsomal stability compare with MBX-2982. Compound27 &32d did not exhibit significant CYP inhibition, hERG binding, and cytotoxicity. Moreover, these compounds lowered the glucose excursion in mice in an oral glucose-tolerance test.