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Bioorg Med Chem Lett. 2015 Oct 15;25(20):4689-92. doi: 10.1016/j.bmcl.2015.06.092. Epub 2015 Jul 3.

Synthesis and biological evaluation of 2-alkyl-2-methoxymethyl-salvinorin ethers as selective κ-opioid receptor agonists.

Author information

1
Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
2
Department of Pharmacology and Center for Substance Abuse Research, School of Medicine, Temple University, 3420 N. Broad Street, Philadelphia, PA 19140, USA.

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.

KEYWORDS:

Affinity; Agonist; Receptor; κ-opioid

PMID:
26330078
PMCID:
PMC4620681
DOI:
10.1016/j.bmcl.2015.06.092
[Indexed for MEDLINE]
Free PMC Article

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