2. Academic Validation
  3. Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52

Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52

  • J Med Chem. 2014 Jun 26;57(12):5226-37. doi: 10.1021/jm5002919.
Masaki Setoh 1,  Naoki Ishii,  Mitsunori Kono,  Yuhei Miyanohana,  Eri Shiraishi,  Toshiya Harasawa,  Hiroyuki Ota,  Tomoyuki Odani,  Naoyuki Kanzaki,  Kazunobu Aoyama,  Teruki Hamada,  Masakuni Kori
Affiliations

Affiliation

  • 1 Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd. , 26-1, Muraoka-higashi-2-chome, Fujisawa, Kanagawa 251-8555, Japan.
PMID: 24884590 DOI: 10.1021/jm5002919
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z