O6C-20-nor-salvinorin A is a stable and potent KOR agonist
[Display omitted] 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...
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Published in | Bioorganic & medicinal chemistry letters Vol. 28; no. 16; pp. 2770 - 2772 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
OXFORD
Elsevier Ltd
01.09.2018
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | [Display omitted]
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 supressed. This new compound, O6C-20-nor-SalA, retains high potency for agonism of KOR. |
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Bibliography: | NIH RePORTER ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2018.01.055 |