Earticle

Design, synthesis and biological evaluation of B-region, known to be a dipolar interacting pharmacophore, modified diarylalkyl amide analogues for novel TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) antagonists was described. A variety of moieties including guanidines, heterocyclic rings, cinnamides, and ${\alpha}$-substituted acetamides were introduced at the B-region. TRPV1 antagonistic activities of these analogues were evaluated by $^{45}Ca^{2+}$ uptake assay in rat DRG neuron. In particular, ${\alpha},{\alpha}$-difluoroamide 53 exhibited 3-fold more potent TRPV1 antagonistic activity ($IC_{50}=0.058{\mu}M$) than the parent amide analogue 6.