N-Isoquinolin-5-yl-N′-aralkyl-urea and -amide antagonists of human vanilloid receptor 1

Starting from a low micromolar agonist lead identified by high-throughput screening, series of N-isoquinolin-5-yl-N′-aralkyl ureas and analogous amides were developed as potent antagonists of human vanilloid receptor 1 (VR1). The synthesis and structure–activity relationships (SAR) of the series are described.