Synthesis and biochemical evaluation of 17-N-beta-aminoalkyl-4,5α-epoxynormorphinans.

ABSTRACT: Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17-N-substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure-activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [³H]DAMGO, [³H]Ile^5,6-deltorphin II and [³H]HS665, respectively. Pharmacological characterization of the compounds in G-protein signaling was determined by [³⁵S]GTPγS bindi

SUBMITTER: Otvos F 

PROVIDER: S-EPMC10660610 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature