Abstract:
: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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Setoh M,Ishii N,Kono M,Miyanohana Y,Shiraishi E,Harasawa T,Ota H,Odani T,Kanzaki N,Aoyama K,Hamada T,Kori Mdoi
10.1021/jm5002919subject
Has Abstractpub_date
2014-06-26 00:00:00pages
5226-37issue
12eissn
0022-2623issn
1520-4804journal_volume
57pub_type
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