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J Med Chem. 2011 Jun 9;54(11):3746-55. doi: 10.1021/jm101621u. Epub 2011 May 16.

Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria.

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  • 1Department of Medicinal Chemistry, University of Utah , Salt Lake City, UT 84112, USA.

Abstract

New compounds nobilamides A-H and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure-activity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogues for treatment of pain.

PMID:
21524089
PMCID:
PMC3133741
DOI:
10.1021/jm101621u
[PubMed - indexed for MEDLINE]
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