Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA.
Abstract:
A new class of kappa-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide kappa agonist 1, ICI 199441. The most active compound identified was ligand 4a (K(i)=0.34 nM), which demonstrated potent antinociceptive activity after oral administration in rodents.