Biarylcarboxybenzamide derivatives as potent vanilloid receptor (VR1) antagonistic ligands

Abstract 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.