title: 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.
authors.affiliation: Roche Palo Alto, Department of Medicinal Chemistry, 3431 Hillview Avenue, Palo Alto, CA 94304-1397, USA. todd.elworthy@roche.com
authors.forename: Todd R
authors.initials: TR
authors.lastname: Elworthy
authors.forename: Emma R
authors.initials: ER
authors.lastname: Brill
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Caires
authors.forename: Woongki
authors.initials: W
authors.lastname: Kim
authors.forename: Leang K
authors.initials: LK
authors.lastname: Lach
authors.forename: Jahari Laurant
authors.initials: JL
authors.lastname: Tracy
authors.forename: San-San
authors.initials: SS
authors.lastname: Chiou
mesh_terms: D007769:Lactams / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D010881:Piperidones / Q000737:chemistry / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype
chemical_list: D007769:Lactams; D008024:Ligands; D010881:Piperidones; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype