Design, synthesis, and biological evaluation of indole derivatives as novel nociceptin/orphanin FQ (N/OFQ) receptor antagonists

A novel series of 2-(1,2,4-oxadiazol-5-yl)-1H-indole derivatives as nociceptin/orphanin FQ (N/OFQ) receptor antagonists was discovered. Systematic modification of our original lead by changing the pendant functional groups, linker, heterocyclic core, and basic side chain revealed the structure–activity requirements for this novel template and resulted in the identification of more potent analog with improved potency as compared to the parent compound.