Novel Potent Antagonists of Transient Receptor Potential Channel, Vanilloid Subfamily Member 1:  Structure−Activity Relationship of 1,3-Diarylalkyl Thioureas Possessing New Vanilloid Equivalents

Recently, 1,3-diarylalkyl thioureas have merged as one of the promising nonvanilloid TRPV1 antagonists possessing excellent therapeutic potential in pain regulation. In this paper, the full structure−activity relationship for TRPV1 antagonism of a novel series of 1,3-diarylalky thioureas is reported. Exploration of the structure−activity relationship, by systemically modulating three essential pharmacophoric regions, led to six examples of 1,3-dibenzyl thioureas, which exhibit Ca2+ uptake inhibition in rat DRG neuron with IC50 between 10 and 100 nM.