Synthesis and biological evaluation of 2-alkyl-2-methoxymethyl-salvinorin ethers as selective κ-opioid receptor agonists.
David Y W Lee, Gang Deng, Zhongze Ma, Wei Xu, Lu Yang, Jing Liu, Ronghua Dai, Lee-Yuan Liu-Chen
Bioorganic & Medicinal Chemistry Letters October 15, 2015 DOI: 10.1016/j.bmcl.2015.06.092 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Measures | Ki, EC50 |
| Topics | Salvia divinorum |
| Keywords | Affinity Agonist Receptor Κ-opioid |
| Key points | A new synthesis enables C-2 alkylation of salvinorin ethers while retaining κ-opioid receptor binding. Among the new compounds, 2-methyl-2-methoxymethyl-salvinorin ether (9a) is reported as a potent full κ agonist with Ki and EC50 values comparable to salvinorin A and U50488H, and the C2-alkylated analogs are identified as full κ agonists. |
Abstract
The synthesis of a new series of C-2-alkyl-2-methoxymethyl-salvinorin ethers and their binding affinities at κ-, μ-, and δ-opioid receptors are presented. We have developed a synthesis that enables installation of alkyl-substituents at C-2 while maintaining the integrity of the C-2 methoxymethyl ether and retaining κ-opioid receptor binding activity. Among these new compounds, 2-methyl-2-methoxymethyl-salvinorin ether (9a) is a potent full agonist at the κ receptor and shows comparable potency in Ki and EC50 with salvinorin A and U50488H. These C2-alkylated analogs have been identified as full κ agonists.
Citations in the library
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