Bioisosteric modification of salvinorin A, a potent and selective kappa-opioid receptor agonist.
D Jeremy Stewart, Hesham Fahmy, Bryan L. Roth, Feng Yan, Jordan K Zjawiony
Arzneimittel-Forschung 2006 DOI: 10.1055/s-0031-1296720 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Intervention | Salvinorin A |
| Topics | Salvia divinorum |
| Key points | Salvinorin A bioisosteres were synthesized and tested for opioid receptor binding and function. The C-2 thioacetate isostere had activity comparable to salvinorin A, nitrogen substitution diminished activity, and intermediates without a C-2 beta-carbonyl had moderate affinity. All derivatives were selective for the kappa-opioid receptor over other opioid subtypes. |
Abstract
Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of 1 were developed and biologically evaluated in binding and functional assays. The C-2 thioacetate isoster produced comparable activity to 1, but nitrogen substitution had a diminishing effect. Intermediates, which lack a beta-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR.
Citations in the library
Cited by 8
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands. Bioorganic & Medicinal Chemistry Letters May 15, 2013
- Selective natural kappa opioid and cannabinoid receptor agonists with a potential role in the treatment of gastrointestinal dysfunction Drug News & Perspectives 2009
- Synthesis of neoclerodane diterpenes and their pharmacological effects. Topics in current chemistry 2011
- CoMFA analyses of C-2 position salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity. Journal of molecular graphics & modelling April 1, 2010
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