New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles

Bioorg Med Chem Lett. 2002 Dec 2;12(23):3487-90. doi: 10.1016/s0960-894x(02)00746-1.

Abstract

A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structure-activity relationships (SARs) of various 3,3-substituents are discussed where it is clear that small alkyl and spiroalkyl groups are required to achieve better PR antagonist activity.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Binding, Competitive
  • Biological Assay
  • Breast Neoplasms
  • Cyclohexanes / chemistry*
  • Cyclohexanes / pharmacology*
  • Decidua / drug effects
  • Female
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Rats
  • Receptors, Progesterone / antagonists & inhibitors*
  • Receptors, Progesterone / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Cyclohexanes
  • Indoles
  • Receptors, Progesterone
  • Alkaline Phosphatase