Lactams as Prostanoid Receptor Ligands. Part 4. 2-Piperidones as Selective EP4 Receptor Agonists.

Abstract 2-Piperidones were prepared bearing heptanoic acid or a thioether heptanoic acid at the 1-position as well as appropriately substituted at the 6-position to mimic the structure of prostaglandins. The stereochemical purity at the 6-position was determined to be ⩾95% ee for an advanced synthetic intermediate. The 2-piperidones were identified as potent agonists at the EP4 prostanoid receptor. They displayed a high affinity (Ki 5–130 nM) at EP4 and subtype selectivity.