11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists

Bioorg Med Chem. 2008 Mar 15;16(6):2753-63. doi: 10.1016/j.bmc.2008.01.010. Epub 2008 Jan 11.

Abstract

Recently, a new class (often referred to as SPRMs: selective progesterone receptor modulators) of progesterone receptor ligands with mixed agonist/antagonist properties has been described. Such compounds are envisaged, for example, as treatment for endometriosis, uterine fibroids, and leiomyomas. Existing SPRMs include Asoprisnil 1 and Uliprisnil acetate 2. In our hands, however, these compounds proved to have a predominantly or exclusively antagonistic in vitro profile, which may make this type of compound less attractive, for example, as contraceptives. We therefore aimed at a class of mixed-profile compounds that would show a more evenly balanced agonist/antagonist profile. A novel class of 11beta-[4-(heteroaryl)phenyl]-substituted pregnanes was identified that displayed the desired balance. Contrary to known SPRMs, this novel class of MPP (mixed-profile progestagen) was found to have a truly mixed activity, including a sizeable agonist component.

MeSH terms

  • Ligands
  • Pregnanes / chemistry
  • Progesterone / agonists
  • Progesterone / antagonists & inhibitors
  • Progesterone / chemistry*
  • Receptors, Progesterone
  • Steroids / chemistry*
  • Structure-Activity Relationship

Substances

  • Ligands
  • Pregnanes
  • Receptors, Progesterone
  • Steroids
  • Progesterone