Semi-synthesis of novel buprenorphine derivatives and their anti-nociceptive properties and dependency potential

Zahra Hasanpour, Peyman Salehi*, Lennart Bunch, Mona Khoramjouy, Morteza Bararjanian, Dan Stærk, Mehrdad Faizi

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)

Abstract

Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine
Original languageEnglish
JournalCanadian Journal of Chemistry
Volume99
Issue number11
Pages (from-to)910-919
ISSN0008-4042
DOIs
Publication statusPublished - 2021

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