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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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-08, Vol.22 (16), p.5227-5231
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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