"A Selective Small Molecule Nociceptin Receptor (NOP) Agonist for the Treatment of Anxiety Disorders"

Research will be presented on Nociceptin receptor (NOP) agonists for the treatment of anxiety related disorders.1 NOP is a member of the opioid subfamily that has homology to other opioid receptors; however it is uniquely different.2 Using a molecular diversity approach, we were able to rapidly advance a library of compounds for biological testing. Through iterative design and analysis of structure activity results, we were able to improve selectivity for NOP over Mu opioid receptor and discover full NOP agonists. A selective (132-fold NOP/Mu) full agonist JNJ- 19385899, compound (1) progressed to clinical studies. The design strategy, synthetic approach and biological data for the related chemical series will be presented.