Synthesis and Pharmacology of a Novel κ Opioid Receptor (KOR) Agonist with a 1,3,5-Trioxazatriquinane Skeleton

  • ACS Med Chem Lett. 2014 Jun 26;5(8):868-72. doi: 10.1021/ml5000542.
Shigeto Hirayama  1 ,  Naohisa Wada  1 ,  Toru Nemoto  1 ,  Takashi Iwai  1 ,  Hideaki Fujii  1 ,  Hiroshi Nagase  1
Affiliations
  • 1. School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
PMID: 25147605 DOI: 10.1021/ml5000542
Abstract

We designed and synthesized the 1,3,5-trioxazatriquinane derivatives with m-hydroxyphenyl groups. These compounds include the phenethylamine structure within them, which is a common structure observed in morphinan derivatives like morphine. Among the synthesized compounds, (-)-8c with two m-hydroxyphenyl groups selectively bound and exerted full agonist activity toward the κ Opioid Receptor (KOR). Subcutaneously administered (-)-8c exhibited significant antinociceptive effects via the KOR in a dose-dependent manner. These results suggest the emergence of a novel class of KOR agonist.

Keywords
Opioid; analgesics; phenethylamine structure.