title: Design and Synthesis of a Piperidinone Scaffold as an Analgesic through Kappa-Opioid Receptor: Structure-Activity Relationship Study of Matrine Alkaloids.
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.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Teramoto
authors.forename: Takayasu
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Terado
authors.forename: Sanae
authors.initials: S
authors.lastname: Odagiri
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kimio
authors.initials: K
authors.lastname: Higashiyama
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007279:Injections, Subcutaneous; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000700:Analgesics; D010880:Piperidines; D017473:Receptors, Opioid, kappa