2. Academic Validation
  3. Synthesis of a novel universal opioid receptor agonist with the 1,3,5-trioxazatriquinane skeleton and its pharmacologies

Synthesis of a novel universal opioid receptor agonist with the 1,3,5-trioxazatriquinane skeleton and its pharmacologies

  • Bioorg Med Chem Lett. 2014 Oct 15;24(20):4895-8. doi: 10.1016/j.bmcl.2014.08.012.
Shigeto Hirayama 1,  Naohisa Wada 1,  Naoya Kuroda 1,  Takashi Iwai 1,  Noriyuki Yamaotsu 1,  Shuichi Hirono 1,  Hideaki Fujii 1,  Hiroshi Nagase 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
  • 2 School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; International Institute for Integrative Sleep Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan. Electronic address: nagase.hiroshi.gt@u.tsukuba.ac.jp.
PMID: 25248680 DOI: 10.1016/j.bmcl.2014.08.012
Abstract

We designed and synthesized of 1,3,5-trioxazatriquinanes with o- or p-hydroxyphenyl rings as analogs of the κ Opioid Receptor Agonist SYK-146 with m-hydroxyphenyl groups. Although almost all tested compounds did not bind to the opioid receptors, only 17b (SYK-524) with two o-hydroxyphenyl rings showed moderate or potent binding affinities and exhibited agonistic activities for the three Opioid Receptor types. Because the basicity of the nitrogen atom in the 1,3,5-trioxazatriquinane structure was predicted to be very low due to the electron withdrawing effect of the three oxygen atoms, SYK-524 was a novel non-morphinan and nonpeptidic opioid universal agonist lacking a basic nitrogen atom.

Keywords

Opioid; Phenethylamine; Universal agonist.

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