Lactams as EP4 prostanoid receptor agonists. 3. Discovery of N-ethylbenzoic acid 2-pyrrolidinones as subtype selective agents.

Two distinct synthetic schemes were applied to access heteroatom-containing α-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP4 receptor activity. γ-Lactams were characterized for their prostanoid EP receptor affinities and EP4 activity and found to be selective for the EP2 and EP4 receptors or selective for the EP4 subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.