- Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52
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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.
- Setoh, Masaki,Ishii, Naoki,Kono, Mitsunori,Miyanohana, Yuhei,Shiraishi, Eri,Harasawa, Toshiya,Ota, Hiroyuki,Odani, Tomoyuki,Kanzaki, Naoyuki,Aoyama, Kazunobu,Hamada, Teruki,Kori, Masakuni
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p. 5226 - 5237
(2014/07/08)
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- AMIDE COMPOUND
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A compound having GPR52 agonist activity or a salt thereof is provided. The compound can be provided as a preventive/therapeutic agent for schizophrenia or the like. The compound is represented by the following formula: wherein A represents —CONRa— or —NRaCO—, Ra represents a hydrogen atom or the like,B represents a hydrogen atom or the like,a ring Cy1 represents a six-membered aromatic ring which may have one or more substituents in addition to a group represented by -A-B,a ring Cy2 represents a six-membered ring which may be substituted with a halogen atom or the like,a ring Cy3 represents a five- or six-membered ring which may have one or more substituents;X represents C1-2 alkylene or the like,m represents an integer of 0 to 2, anda ring Cy4 represents a six-membered aromatic ring which may have one or more substituents.
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Page/Page column 69
(2010/03/04)
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