Discovery of orally active, pyrrolidinone-based progesterone receptor partial agonists

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4664-8. doi: 10.1016/j.bmcl.2009.06.081. Epub 2009 Jun 25.

Abstract

We have designed and synthesized a novel series of pyrrolidinones as progesterone receptor partial agonists. Compounds from this series had improved AR selectivity, rat pharmacokinetic properties, and in vivo potency compared to the lead compound. In addition, these compounds had improved selectivity against hERG channel inhibition.

MeSH terms

  • Administration, Oral
  • Animals
  • Binding Sites
  • Drug Discovery
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Haplorhini
  • Humans
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / chemistry*
  • Pyrrolidinones / pharmacokinetics
  • Rats
  • Receptors, Progesterone / agonists*
  • Receptors, Progesterone / metabolism
  • Structure-Activity Relationship

Substances

  • Ether-A-Go-Go Potassium Channels
  • KCNH1 protein, human
  • Pyrrolidinones
  • Receptors, Progesterone