Design and synthesis of novel orexin antagonists via structural simplification of the morphinan skeleton

Sayaka Ohrui, Yoko Irukayama-Tomobe, Yukiko Ishikawa, Masashi Yanagisawa, Hiroshi Nagase

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalHeterocycles
Volume103
Issue number2
DOIs
StatePublished - 2021

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

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