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

[Image: see text] TAK-925, a potent, selective, and brain-penetrant orexin 2 receptor (OX2R) agonist, [methyl (2R,3S)-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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fujimoto, Tatsuhiko, Rikimaru, Kentaro, Fukuda, Koichiro, Sugimoto, Hiromichi, Masuda, Kei, Ohyabu, Norio, Banno, Yoshihiro, Tokunaga, Norihito, Kawamoto, Tetsuji, Tomata, Yoshihide, Kumagai, Yasumi, Iida, Motoo, Nagano, Yoichi, Yoneyama-Hirozane, Mariko, Shimizu, Yuji, Sasa, Katsunori, Ishikawa, Takashi, Yukitake, Hiroshi, Ito, Mitsuhiro, Aoyama, Kazunobu, Matsumoto, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919389/
https://www.ncbi.nlm.nih.gov/pubmed/35295087
http://dx.doi.org/10.1021/acsmedchemlett.1c00626
_version_ 1784668933424414720
author Fujimoto, Tatsuhiko
Rikimaru, Kentaro
Fukuda, Koichiro
Sugimoto, Hiromichi
Masuda, Kei
Ohyabu, Norio
Banno, Yoshihiro
Tokunaga, Norihito
Kawamoto, Tetsuji
Tomata, Yoshihide
Kumagai, Yasumi
Iida, Motoo
Nagano, Yoichi
Yoneyama-Hirozane, Mariko
Shimizu, Yuji
Sasa, Katsunori
Ishikawa, Takashi
Yukitake, Hiroshi
Ito, Mitsuhiro
Aoyama, Kazunobu
Matsumoto, Takahiro
author_facet Fujimoto, Tatsuhiko
Rikimaru, Kentaro
Fukuda, Koichiro
Sugimoto, Hiromichi
Masuda, Kei
Ohyabu, Norio
Banno, Yoshihiro
Tokunaga, Norihito
Kawamoto, Tetsuji
Tomata, Yoshihide
Kumagai, Yasumi
Iida, Motoo
Nagano, Yoichi
Yoneyama-Hirozane, Mariko
Shimizu, Yuji
Sasa, Katsunori
Ishikawa, Takashi
Yukitake, Hiroshi
Ito, Mitsuhiro
Aoyama, Kazunobu
Matsumoto, Takahiro
author_sort Fujimoto, Tatsuhiko
collection PubMed
description [Image: see text] TAK-925, a potent, selective, and brain-penetrant orexin 2 receptor (OX2R) agonist, [methyl (2R,3S)-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.
format Online
Article
Text
id pubmed-8919389
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-89193892022-03-15 Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist Fujimoto, Tatsuhiko Rikimaru, Kentaro Fukuda, Koichiro Sugimoto, Hiromichi Masuda, Kei Ohyabu, Norio Banno, Yoshihiro Tokunaga, Norihito Kawamoto, Tetsuji Tomata, Yoshihide Kumagai, Yasumi Iida, Motoo Nagano, Yoichi Yoneyama-Hirozane, Mariko Shimizu, Yuji Sasa, Katsunori Ishikawa, Takashi Yukitake, Hiroshi Ito, Mitsuhiro Aoyama, Kazunobu Matsumoto, Takahiro ACS Med Chem Lett [Image: see text] TAK-925, a potent, selective, and brain-penetrant orexin 2 receptor (OX2R) agonist, [methyl (2R,3S)-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. American Chemical Society 2022-02-04 /pmc/articles/PMC8919389/ /pubmed/35295087 http://dx.doi.org/10.1021/acsmedchemlett.1c00626 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Fujimoto, Tatsuhiko
Rikimaru, Kentaro
Fukuda, Koichiro
Sugimoto, Hiromichi
Masuda, Kei
Ohyabu, Norio
Banno, Yoshihiro
Tokunaga, Norihito
Kawamoto, Tetsuji
Tomata, Yoshihide
Kumagai, Yasumi
Iida, Motoo
Nagano, Yoichi
Yoneyama-Hirozane, Mariko
Shimizu, Yuji
Sasa, Katsunori
Ishikawa, Takashi
Yukitake, Hiroshi
Ito, Mitsuhiro
Aoyama, Kazunobu
Matsumoto, Takahiro
Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
title Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
title_full Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
title_fullStr Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
title_full_unstemmed Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
title_short Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
title_sort discovery of tak-925 as a potent, selective, and brain-penetrant orexin 2 receptor agonist
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919389/
https://www.ncbi.nlm.nih.gov/pubmed/35295087
http://dx.doi.org/10.1021/acsmedchemlett.1c00626
work_keys_str_mv AT fujimototatsuhiko discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT rikimarukentaro discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT fukudakoichiro discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT sugimotohiromichi discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT masudakei discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT ohyabunorio discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT bannoyoshihiro discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT tokunaganorihito discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT kawamototetsuji discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT tomatayoshihide discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT kumagaiyasumi discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT iidamotoo discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT naganoyoichi discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT yoneyamahirozanemariko discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT shimizuyuji discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT sasakatsunori discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT ishikawatakashi discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT yukitakehiroshi discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT itomitsuhiro discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT aoyamakazunobu discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist
AT matsumototakahiro discoveryoftak925asapotentselectiveandbrainpenetrantorexin2receptoragonist

Ejemplares similares