The SAR analysis of TRPV1 agonists with the α-methylated B-region

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Abstract

A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding α-methylated analogues were investigated. Whereas the α-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding.

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Acknowledgments

This research was supported by Grants R11-2007-107-02001-0 from the NRF and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270). We thank other members of the Blumberg group for assistance with some of the assays.

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