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Design, synthesis and biological evaluation of B-region modified diarylalkyl amide analogues as novel TRPV1 antagonists

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Abstract

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 α-substituted acetamides were introduced at the B-region. TRPV1 antagonistic activities of these analogues were evaluated by 45Ca2+ uptake assay in rat DRG neuron. In particular, α,α-difluoroamide 53 exhibited 3-fold more potent TRPV1 antagonistic activity (IC50 = 0.058 μM) than the parent amide analogue 6.

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Acknowledgments

This research work was supported by grant from the Basic Research Program of the Korea Science, and supported in part by the grant from the Natural Science Foundation of Fujian Province of China (Grant No. 2011J01257).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Xiamen University, Xiang’an South Road, Xiamen, 361102, People’s Republic of China

    Shao-Mei Yang, Xiao-Yuan Wang & Fu-Nan Li

  2. College of Pharmacy, Woosuk University, Wanju, 565-701, Republic of Korea

    Young Taek Han

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  1. Young Taek Han
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  2. Shao-Mei Yang
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Correspondence to Fu-Nan Li.

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Han, Y.T., Yang, SM., Wang, XY. et al. Design, synthesis and biological evaluation of B-region modified diarylalkyl amide analogues as novel TRPV1 antagonists. Arch. Pharm. Res. 37, 440–451 (2014). https://doi.org/10.1007/s12272-013-0228-x

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