O6C-20-nor-SalA is a stable and potent KOR agonist
Ryan A Shenvi, Shun Hirasawa, Min Cho, Tarsis F. Brust, Jeremy J Roach, Larua M. Bohn
ChemRxiv December 27, 2017 preprint DOI: 10.26434/chemrxiv.5728286.v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Citations | 1 |
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| Key points | Replacing C20 with hydrogen and O6 with CH2 in Salvinorin A suppresses C8 epimerization entirely, and the resulting compound, O6C-20-nor-SalA, retains high potency for kappa-opioid receptor agonism. |
Abstract
Salvinorin A (SalA) is a potent and selective agonist of the kappa-opioid receptor (KOR), but its instability has frustrated medicinal chemistry efforts. Treatment of SalA with weak bases like DBU leads to C8 epimerization with loss of receptor affinity and signaling potency. Here we show that replacement of C20 with H and replacement of O6 with CH2 stabilizes the SalA scaffold relative to its C8 epimer, so much so that epimerization is completely suppressed. This new compound, O6C-20-nor-SalA, retains high potency for agonism of KOR.