The SAR analysis of TRPV1 agonists with the [alpha]-methylated B-region

A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding [alpha]-methylated analogues were investigated. Whereas the [alpha]-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2012-08, Vol.22 (16), p.5227-5231
Main Authors: Cho, Yongsung, Kim, Myeong Seop, Kim, Ho Shin, Ann, Jihyae, Lee, Jiyoun, Pearce, Larry V, Pavlyukovets, Vladimir A, Morgan, Matthew A, Blumberg, Peter M, Lee, Jeewoo
Format: Article
Language:English
Subjects:
amides
Capsaicin receptors
Hydrogen bonding
thiourea
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Summary:A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding [alpha]-methylated analogues were investigated. Whereas the [alpha]-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.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2012.06.059