Basic Research Program of the Korea Science; Natural Science Foundation of Fujian Province of China [2011J01257]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 Ca-45(2+) uptake assay in rat DRG neuron. In particular, alpha,alpha-difluoroamide 53 exhibited 3-fold more potent TRPV1 antagonistic activity (IC50 = 0.058 mu M) than the parent amide analogue 6
