Structure–activity relationships of the prototypical TRPM8 agonist icilin

[Display omitted] A series of structural analogues of the TRPM8 agonist icilin was prepared. The compounds were examined for their ability to exert agonist or antagonist effects in HEK-293 cells expressing the TRPM8 receptor. Most structural modifications of the icilin structure largely met with dim...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2015-06, Vol.25 (11), p.2285-2290
Main Authors: De Petrocellis, Luciano, Ortar, Giorgio, Schiano Moriello, Aniello, Serum, Eric M., Rusterholz, David B.
Format: Article
Language:English
Subjects:
HEK293 Cells
Humans
Icilin
Molecular Structure
Pyrimidinones - chemistry
Pyrimidinones - pharmacology
Structure-Activity Relationship
Thermo-TRP channels
TRPM Cation Channels - agonists
TRPM8
TRPV1
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Summary:[Display omitted] A series of structural analogues of the TRPM8 agonist icilin was prepared. The compounds were examined for their ability to exert agonist or antagonist effects in HEK-293 cells expressing the TRPM8 receptor. Most structural modifications of the icilin structure largely met with diminished TRPM8 agonist activity. Cinnamamide ‘open-chain’ analogs of icilin, however, demonstrated significant antagonistic actions at the TRPM8 receptor. Optimal potency (IC50=73nM) was observed in the 3-iodo derivative 18l.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2015.04.032