Novel pyridone EP4 agonists featuring allylic alcohol ω-chains

Bioorg Med Chem Lett. 2020 May 15;30(10):127104. doi: 10.1016/j.bmcl.2020.127104. Epub 2020 Mar 10.

Abstract

Novel prostaglandin E2 receptor 4 (EP4) agonists featuring a pyridone core and an allylic alcohol ω-chain were discovered. These agonists were shown to be selective over EP1, EP2 and EP3. Analogs harboring a 4-carboxylic acid phenethyl α-chain displayed improved potency over those containing an n-heptanoic acid chain. Key SAR relationships were also identified.

Keywords: Agonists; Allylic alcohol; Prostaglandin E2 receptor 4 (EP(4)); Pyridone.

MeSH terms

  • Humans
  • Propanols / chemistry*
  • Propanols / metabolism
  • Protein Isoforms / agonists
  • Protein Isoforms / metabolism
  • Pyridones / chemistry*
  • Pyridones / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype / agonists*
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism
  • Structure-Activity Relationship

Substances

  • Propanols
  • Protein Isoforms
  • Pyridones
  • Receptors, Prostaglandin E, EP4 Subtype
  • allyl alcohol