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=73 nM) was observed in the 3-iodo derivative 18l.
Keywords: Icilin; TRPM8; TRPV1; Thermo-TRP channels.
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