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The transient receptor potential TRP family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients.
We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans. Synthetic details for all compounds described.
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