1-Methyl-1H-pyrrole-2-carbonitrile containing tetrahydronaphthalene derivatives as non-steroidal progesterone receptor antagonists

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4816-8. doi: 10.1016/j.bmcl.2010.06.109. Epub 2010 Jun 25.

Abstract

Non-steroidal 1-methyl-1H-pyrrole-2-carbonitrile containing tetrahydronaphthalenes and acyclic derivatives were evaluated as novel series of progesterone receptor (PR) antagonists using the T47D cell alkaline phosphatase assay. Moderate to potent PR antagonists were achieved with these scaffolds. Several compounds (e.g., 15 and 20) demonstrated low nanomolar PR antagonist potency and good selectivity versus other steroid receptors.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Cell Line, Tumor
  • Humans
  • Pyrroles / chemistry*
  • Receptors, Progesterone / antagonists & inhibitors*
  • Receptors, Progesterone / metabolism
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / chemical synthesis
  • Tetrahydronaphthalenes / chemistry*
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Pyrroles
  • Receptors, Progesterone
  • Tetrahydronaphthalenes
  • Alkaline Phosphatase