Novel potent antagonists of transient receptor potential channel, vanilloid subfamily member 1: structure-activity relationship of 1,3-diarylalkyl thioureas possessing new vanilloid equivalents.
Recently, 1,3-diarylalkyl thioureas have merged as one of the promising nonvanilloid TRPV1 antagonists possessing excellent therapeutic potential in pain regulation. In this paper, the full structure-activity relationship for TRPV1 antagonism of a novel series of 1,3-diarylalky thioureas is reported. Exploration of the structure-activity relationship, by systemically modulating three essential pharmacophoric regions, led to six examples of 1,3-dibenzyl thioureas, which exhibit Ca(2+) uptake inhibition in rat DRG neuron with IC(50) between 10 and 100 nM.
Suh
Young-Ger
YG
College of Pharmacy, and Sensory Research Center, CRI, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea. ygsuh@snu.ac.kr
Lee
Yong-Sil
YS
Min
Kyung-Hoon
KH
Park
Ok-Hui
OH
Kim
Jin-Kwan
JK
Seung
Ho-Sun
HS
Seo
Seung-Yong
SY
Lee
Bo-Young
BY
Nam
Yeon-Hee
YH
Lee
Kwang-Ok
KO
Kim
Hee-Doo
HD
Park
Hyeung-Geun
HG
Lee
Jeewoo
J
Oh
Uhtaek
U
Lim
Ju-Ok
JO
Kang
Sang-Uk
SU
Kil
Min-Jung
MJ
Koo
Jae-Yeon
JY
Shin
Song Seok
SS
Joo
Yung-Hyup
YH
Kim
Jin Kwan
JK
Jeong
Yeon-Su
YS
Kim
Sun-Young
SY
Park
Young-Ho
YH
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D007473:Ion Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013890:Thiourea; D002118:Calcium