Design, synthesis, and biological evaluation of C₆-difluoromethylenated epoxymorphinan Mu opioid receptor antagonists.

ABSTRACT: The recent widespread abuse of high potency synthetic opioids, such as fentanyl, presents a serious threat to individuals affected by substance use disorder. Synthetic opioids generally exhibit prolonged in vivo circulatory half-lives that can outlast the reversal effects of conventional naloxone-based overdose antidotes leading to a life-threatening relapse of opioid toxicity known as renarcotization. In this manuscript, we present our efforts to combat the threat of renarcotization by attempting to extend the half-life of traditional MOR antagonists through the design of novel, fluorinated 4,5-epoxymorphinans possessing increased lipophilicity. Analogues were prepared via a concise synthetic strategy highlighted by decarboxylative Wittig olefination of the C₆ ket

SUBMITTER: Kassick AJ 

PROVIDER: S-EPMC8864491 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature