Synthesis and biological evaluation of 2-alkyl-2-methoxymethyl-salvinorin ethers as selective κ-opioid receptor agonists. Issue 20 (15th October 2015)

• Record Type: Journal Article
• Authors: Lee, David Y.W.; Deng, Gang; Ma, Zhongze; Xu, Wei; Yang, Lu; Liu, Jing; Dai, Ronghua; Liu-Chen, Lee-Yuan
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 20(2015)
• Page Start: 4689
• Page End: 4692
• Publication Date: 2015-10-15
• Subjects: κ-opioid -- Receptor -- Affinity -- Agonist; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.06.092
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.