Literature DB >> 25147605

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

Shigeto Hirayama1, Naohisa Wada1, Toru Nemoto1, Takashi Iwai1, Hideaki Fujii1, Hiroshi Nagase1.   

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.

Entities:  

Keywords:  Opioid; analgesics; phenethylamine structure

Year:  2014        PMID： 25147605      PMCID： PMC4137376          DOI： 10.1021/ml5000542

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  20 in total

Review 1.  3D-pharmacophore identification for kappa-opioid agonists using ligand-based drug-design techniques.

Authors:  Noriyuki Yamaotsu; Shuichi Hirono
Journal:  Top Curr Chem       Date:  2011

2.  Analgesics and their antagonists: some steric and chemical considerations. I. The dissociation constants of some tertiary amines and synthetic analgesics, the conformations of methadone-type compounds.

Authors:  A H BECKETT
Journal:  J Pharm Pharmacol       Date:  1956-11       Impact factor: 3.765

3.  Identification of the three-dimensional pharmacophore of kappa-opioid receptor agonists.

Authors:  Noriyuki Yamaotsu; Hideaki Fujii; Hiroshi Nagase; Shuichi Hirono
Journal:  Bioorg Med Chem       Date:  2010-04-28       Impact factor: 3.641

4.  Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at mu, delta, and kappa opioid receptors.

Authors:  Xuemei Peng; Brian I Knapp; Jean M Bidlack; John L Neumeyer
Journal:  J Med Chem       Date:  2006-01-12       Impact factor: 7.446

Review 5.  Twin and triplet drugs in opioid research.

Authors:  Hideaki Fujii
Journal:  Top Curr Chem       Date:  2011

6.  Effect of beta-funaltrexamine on opioid side-effects produced by morphine and U-50, 488H.

Authors:  A G Hayes; M Skingle; M B Tyers
Journal:  J Pharm Pharmacol       Date:  1985-11       Impact factor: 3.765

7.  Pharmacological profiles of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) on the mouse vas deferens preparation.

Authors:  S J Ward; P S Portoghese; A E Takemori
Journal:  Eur J Pharmacol       Date:  1982-06-04       Impact factor: 4.432

8.  Effects of beta-funaltrexamine (beta-FNA) on morphine dependence in rats and monkeys.

Authors:  M D Aceto; W L Dewey; P S Portoghese; A E Takemori
Journal:  Eur J Pharmacol       Date:  1986-04-29       Impact factor: 4.432

9.  Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet).

Authors:  Naohisa Wada; Hideaki Fujii; Koji Koyano; Shigeto Hirayama; Takashi Iwai; Toru Nemoto; Hiroshi Nagase
Journal:  Bioorg Med Chem Lett       Date:  2012-10-13       Impact factor: 2.823

10.  Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective κ opioid receptor agonist.

Authors:  Mariana Spetea; Ilona P Berzetei-Gurske; Elena Guerrieri; Helmut Schmidhammer
Journal:  J Med Chem       Date:  2012-11-07       Impact factor: 7.446
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  2 in total

1.  Asymmetric [3 + 2] cycloaddition of donor-acceptor aziridines with aldehydes via carbon-carbon bond cleavage.

Authors:  Yuting Liao; Xiaohua Liu; Yu Zhang; Yali Xu; Yong Xia; Lili Lin; Xiaoming Feng
Journal:  Chem Sci       Date:  2016-02-23       Impact factor: 9.825

2.  Structurally Related Kappa Opioid Receptor Agonists with Substantial Differential Signaling Bias: Neuroendocrine and Behavioral Effects in C57BL6 Mice.

Authors:  Amelia D Dunn; Brian Reed; Catherine Guariglia; Alexandra M Dunn; Joshua M Hillman; Mary Jeanne Kreek
Journal:  Int J Neuropsychopharmacol       Date:  2018-09-01       Impact factor: 5.176
  2 in total

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