2. Academic Validation
  3. Novel delta opioid receptor agonists with oxazatricyclodecane structure

Novel delta opioid receptor agonists with oxazatricyclodecane structure

  • ACS Med Chem Lett. 2014 Jan 27;5(4):368-72. doi: 10.1021/ml400491k.
Hideaki Fujii 1,  Kohei Hayashida 1,  Akiyoshi Saitoh 2,  Akinobu Yokoyama 3,  Shigeto Hirayama 1,  Takashi Iwai 1,  Eriko Nakata 4,  Toru Nemoto 1,  Yuka Sudo 3,  Yasuhito Uezono 5,  Mitsuhiko Yamada 2,  Hiroshi Nagase 1
Affiliations

Affiliations

  • 1 School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
  • 2 Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry , 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
  • 3 Division of Cancer Pathophysiology, National Cancer Center Research Institute , 5-1-1 Tsukiji, Tokyo 104-0045, Japan ; Faculty of Pharmaceutical Science, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 274-8510, Japan.
  • 4 Discovery Research Laboratories, Nippon Chemiphar Co., Ltd. , 1-22 Hikokawado, Misato, Saitama 341-0005, Japan.
  • 5 Division of Cancer Pathophysiology, National Cancer Center Research Institute , 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
PMID: 24900842 DOI: 10.1021/ml400491k
Abstract

We synthesized compounds 4a,c-f,h,i containing the oxazatricyclodecane structure from a novel rearrangement reaction product 2a. All the prepared compounds 4a,c-f,h,i exhibited full agonistic activities for the δ Opioid Receptor (DOR). Among them, the N-methyl derivative 4c was highly selective, and the most effective DOR agonist in functional assays. Subcutaneous administration of 4c produced dose-dependent and NTI (selective DOR antagonist)-reversible antinociception lacking any convulsive behaviors in the mice acetic acid writhing tests. The N-methyl derivative 4c is expected to be a promising lead compound for selective DOR agonists with a novel chemotype.

Keywords

CellKey; DOR; Opioid; oxazatricyclodecane structure.

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