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

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 thioure...

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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 - chemical synthesis
Amides - chemistry
Amides - metabolism
Biological and medical sciences
Capsaicin
Medical sciences
Methylation
Pharmacology. Drug treatments
Protein Binding
Stereoisomerism
Structure-Activity Relationship
Thiourea - chemical synthesis
Thiourea - chemistry
Thiourea - metabolism
TRPV Cation Channels - agonists
TRPV Cation Channels - metabolism
TRPV1 agonist
Vanilloid receptor 1
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.06.059