Design and Synthesis of a Piperidinone Scaffold as an Analgesic through Kappa-Opioid Receptor: Structure–Activity Relationship Study of Matrine Alkaloids

Hiroyoshi Teramoto; Takayasu Yamauchi; Yasushi Terado; Sanae Odagiri; Shigeru Sasaki; Kimio Higashiyama

doi:10.1248/cpb.c15-00962

Regular Articles

Design and Synthesis of a Piperidinone Scaffold as an Analgesic through Kappa-Opioid Receptor: Structure–Activity Relationship Study of Matrine Alkaloids

Hiroyoshi Teramoto, Takayasu Yamauchi , Yasushi Terado, Sanae Odagiri, Shigeru Sasaki, Kimio Higashiyama

Author information

Keywords: antinociception, kappa opioid receptor (KOR), matrine, piperidone, acetic acid-induced abdominal contraction test, mouse

JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary material

2016 Volume 64 Issue 5 Pages 410-419

DOI https://doi.org/10.1248/cpb.c15-00962

Details

Abstract

The matrine-type alkaloid 4-dimethylamino-1-pentanoylpiperidine (3a) has an antinociceptive effect through its impact on the κ-opioid receptor (KOR). Derivatives of 3a were synthesized by altering its amide and tertiary amine groups, and were evaluated for their antinociceptive effects. The results indicated that the distance between these groups on 3a was optimal for the antinociceptive effect. The effects obtained with compounds 8 and 9 indicated that the relative configuration of the 3- and 4-substituents influenced the effect mediated through the KOR.

Graphical Abstract Fullsize Image

Corresponding author

Register with J-STAGE for free!