1207965-12-5Relevant articles and documents
Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52
Setoh, Masaki,Ishii, Naoki,Kono, Mitsunori,Miyanohana, Yuhei,Shiraishi, Eri,Harasawa, Toshiya,Ota, Hiroyuki,Odani, Tomoyuki,Kanzaki, Naoyuki,Aoyama, Kazunobu,Hamada, Teruki,Kori, Masakuni
, p. 5226 - 5237 (2014/07/08)
G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A series of GPR52 agonists with a bicyclic core was designed to fix the conformation of the phenethyl ether moiety of compounds 2a and 2b. 3-[2-(3-Chloro-5-fluorobenzyl)-1-benzothiophen-7-yl]-N- (2-methoxyethyl)benzamide 7m showed potent activity (pEC50 = 7.53 ± 0.08) and good pharmacokinetic properties. Compound 7m significantly suppressed methamphetamine-induced hyperactivity in mice after oral administration of 3 mg/kg without disturbance of motor function.