Discovery of novel arylpyrazole series as potent and selective opioid receptor-like 1 (ORL1) antagonists.

Abstract The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure–activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31 , (1 S ,3 R )- N -{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1 H -pyrazol-3-yl]methyl}-3-fluorocyclopentanamine, which exhibits high intrinsic potency and selectivity against other opioid receptors and hERG potassium channel.