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

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 ? 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.

SUBMITTER: Hirayama S

PROVIDER: S-EPMC4137376 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Hirayama Shigeto S Wada Naohisa N Nemoto Toru T Iwai Takashi T Fujii Hideaki H Nagase Hiroshi H

ACS medicinal chemistry letters 20140626 8

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 d ...[more]

PMID: 25147605

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Agonist-promoted kappa opioid receptor (KOR) phosphorylation has behavioral endpoint-dependent and sex-specific effects.

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