title: Novel delta opioid receptor agonists with oxazatricyclodecane structure.
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.
authors.affiliation: School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hayashida
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry , 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: 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.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.affiliation: School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwai
authors.affiliation: Discovery Research Laboratories, Nippon Chemiphar Co., Ltd. , 1-22 Hikokawado, Misato, Saitama 341-0005, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Nakata
authors.affiliation: School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: 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.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sudo
authors.affiliation: Division of Cancer Pathophysiology, National Cancer Center Research Institute , 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry , 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.affiliation: School of Pharmacy, Kitasato University , 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
keywords: CellKey; DOR; Opioid; oxazatricyclodecane structure