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Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist.

Authors :
Fujimoto T
Rikimaru K
Fukuda K
Sugimoto H
Masuda K
Ohyabu N
Banno Y
Tokunaga N
Kawamoto T
Tomata Y
Kumagai Y
Iida M
Nagano Y
Yoneyama-Hirozane M
Shimizu Y
Sasa K
Ishikawa T
Yukitake H
Ito M
Aoyama K
Matsumoto T
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 Feb 04; Vol. 13 (3), pp. 457-462. Date of Electronic Publication: 2022 Feb 04 (Print Publication: 2022).
Publication Year :
2022

Abstract

TAK-925, a potent, selective, and brain-penetrant orexin 2 receptor (OX2R) agonist, [methyl (2 R ,3 S )-3-((methylsulfonyl)amino)-2-((( cis -4-phenylcyclohexyl)oxy)methyl)piperidine-1-carboxylate, 16 ], was identified through the optimization of compound 2 , which was discovered by a high throughput screening (HTS) campaign. Subcutaneous administration of compound 16 produced wake-promoting effects in mice during the sleep phase. Compound 16 (TAK-925) is being developed for the treatment of narcolepsy and other related disorders.<br />Competing Interests: The authors declare no competing financial interest.<br /> (© 2022 The Authors. Published by American Chemical Society.)

Details

Language :
English
ISSN :
1948-5875
Volume :
13
Issue :
3
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
35295087
Full Text :
https://doi.org/10.1021/acsmedchemlett.1c00626