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 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.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Yongsung
Y
Cho
Myeong Seop
MS
Kim
Ho Shin
HS
Kim
Jihyae
J
Ann
Jiyoun
J
Lee
Larry V
LV
Pearce
Vladimir A
VA
Pavlyukovets
Matthew A
MA
Morgan
Peter M
PM
Blumberg
Jeewoo
J
Lee
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008745:Methylation; D011485:Protein Binding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000819:agonists* / Q000378:metabolism; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D000577:Amides; D050916:TRPV Cation Channels; D013890:Thiourea