Design and synthesis of novel and potent GPR119 agonists with a spirocyclic structure. Issue 7 (15th April 2018)

• Record Type: Journal Article
• Authors: Harada, Kazuhito; Mizukami, Jun; Kadowaki, Sho; Matsuda, Isamu; Watanabe, Takashi; Oe, Yasuhiro; Kodama, Yoshitoshi; Aoki, Kenta; Suwa, Katsunori; Fukuda, Sumiaki; Yata, Shinji; Inaba, Takashi
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 7(2018)
• Page Start: 1228
• Page End: 1233
• Publication Date: 2018-04-15
• Subjects: GPR119 agonist -- Spirocyclic structure -- Type 2 diabetes; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.02.044
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Exploration of alternative structures of the substituted piperidine or piperazine ring which are characteristic in most of the reported GPR119 agonists provided novel spirocyclic cyclohexane derivatives. The representative17 with a high three-dimensionality exhibited potent agonistic activity (EC50 = 4 nM) with no CYP inhibitory activity (IC50 >10 μM). Compound17 also displayed hypoglycemic activity with insulin secretion dependent on glucose concentration in an intraperitoneal glucose tolerance test in rats.