@article{35327e6c93604a7ba2d2c21ff767bf1c,
title = "Design and synthesis of novel orexin antagonists via structural simplification of the morphinan skeleton",
abstract = "Herein, we report novel orexin antagonists with a spiro-type piperidine skeleton designed and synthesized via removal of the unnecessary sites of orexin 1 receptor (OX1R) antagonists with a morphinan skeleton for binding to OX1R. In addition, while decahydroisoquinoline compounds with an A-ring did not show antagonistic activity for OX1R, spiro-type piperidine compounds with a dihydroindene structure showed antagonistic activities. This suggests that the lipophilic site corresponding to the A-ring of the morphinan skeleton is important for determining the antagonistic activity toward OX1R.",
author = "Sayaka Ohrui and Yoko Irukayama-Tomobe and Yukiko Ishikawa and Masashi Yanagisawa and Hiroshi Nagase",
note = "Funding Information: We are grateful to Prof. Tomohiko Ohwada (The University of Tokyo) for his kind and helpful discussions. We thank Prof. Shuji Akai (Osaka University), Prof. Masayuki Inoue (The University of Tokyo), Prof. Takeo Kawabata (Kyoto University), Dr. Mitsuaki Ohtani (ITSUU Laboratory), and Dr. Kin-ichi Tadano (ITSUU Laboratory) for their kind and helpful discussions. We would like to thank the members of the SBDD Group of the Drug Discovery Chemistry Laboratory, Shionogi Pharmaceutical Co., Ltd. for conducting the crystal structure analysis. We also thank for Dr. Nagumo Yasuyuki (The University of Tsukuba) for his kind and support. Publisher Copyright: {\textcopyright} 2021 Japan Institute of Heterocyclic Chemistry. All rights reserved.",
year = "2021",
doi = "10.3987/COM-20-S(K)63",
language = "English (US)",
volume = "103",
journal = "Heterocycles",
issn = "0385-5414",
publisher = "Japan Institute of Heterocyclic Chemistry",
number = "2",
}