Biarylcarboxybenzamide derivatives as potent vanilloid receptor (VR1) antagonistic ligands.
Seventeen biarylcarboxybenzamide derivatives were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor (VR1) in rat DRG neurons. The replacement of the piperazine moiety of the lead compound 1 with phenyl ring showed quite enhanced antagonistic activity. Among the prepared derivatives, N-(4-tert-butylphenyl)-4-pyridine-2-yl-benzamide (2, IC(50)=31 nM) and N-(4-tert-butylphenyl)-4-(3-methylpyridine-2-yl)benzamide (3g, IC(50)=31 nM), showed 5-fold higher antagonistic activity than 1 in (45)Ca(2+)-influx assay.
Park
Hyeung-Geun
HG
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. hgpk@plaza.snu.ac.kr
Choi
Ji-Yeon
JY
Kim
Mi-Hyun
MH
Choi
Sea-Hoon
SH
Park
Mi-Kyung
MK
Lee
Jihye
J
Suh
Young-Ger
YG
Cho
Hawon
H
Oh
Uhtaek
U
Kim
Hee-Doo
HD
Joo
Yung Hyup
YH
Shin
Song Seok
SS
Kim
Jin Kwan
JK
Jeong
Yeon Su
YS
Koh
Hyun-Ju
HJ
Park
Young-Ho
YH
Jew
Sang-Sup
SS
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology; D020128:Inhibitory Concentration 50; D007473:Ion Channels / Q000819:agonists / Q000037:antagonists & inhibitors*; D008024:Ligands; D009474:Neurons; D051381:Rats; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels
D001549:Benzamides; D007473:Ion Channels; D008024:Ligands; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat