952182-78-4Relevant articles and documents
Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists
Tokumaru, Kazuyuki,Ito, Yoshiteru,Nomura, Izumi,Nakahata, Takashi,Shimizu, Yuji,Kurimoto, Emi,Aoyama, Kazunobu,Aso, Kazuyoshi
, p. 3098 - 3115 (2017/05/24)
G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (4u; half maximal effective concentration (EC50)?=?75?nM, maximal response (Emax)?=?122%) starting from a high-throughput screening hit 3 (EC50?=?470?nM, Emax?=?56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists. A structure–activity relationship study of 4-azolylbenzamide resulted in the design of the 1,2,4-triazole derivative 4u, which demonstrated excellent bioavailability in rats (F?=?53.8%). Oral administration of 4u (10?mg/kg) significantly suppressed methamphetamine-induced hyperlocomotion in mice. Thus, 4u is a promising lead compound for drug discovery research of GPR52 agonists.
THIAZOLE DERIVATIVE
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Page/Page column 83, (2012/12/14)
Provided is a compound having an agonist action on GPR52, which is useful as a prophylactic or therapeutic drug for mental diseases such as schizophrenia and the like, and the like. A compound represented by the formula (I): wherein each symbol is as defi
