Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists.

Abstract The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H 4 receptor inverse agonists is described. The initial hit, 3A (IC 50 19 nM) was identified by means of a ligand-based virtual screening approach. Subsequent medicinal chemistry exploration yielded 18I which possessed increased potency ( R -enantiomer IC 50 1 nM) as well as enhanced microsomal stability.