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.