Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization.

Abstract A series of 7-[(5 R )-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP 4 receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17 , 24 , 30 , 31 , and 33 ) of high potency and greater than 1000-fold affinity for EP 4 versus the other EP prostanoid receptors.