Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors

J Med Chem. 1995 Dec 8;38(25):4880-4. doi: 10.1021/jm00025a004.

Abstract

A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity relationships were developed for a set of these compounds, and a representative analog 1-(3,4-dichlorobenzoyl)-3-phenyl-1,4,5,6-tetrahydropyridazine++ + (1i, RWJ 25333) was chosen for further evaluation. RWJ 25333 stimulated the in vitro proliferation of human osteoblast-like cells but not human breast cells.

MeSH terms

  • Bone Neoplasms
  • Bone and Bones / metabolism*
  • Breast Neoplasms
  • Drug Design
  • Female
  • Humans
  • Ligands
  • Progestins / metabolism
  • Pyridazines / chemical synthesis
  • Pyridazines / chemistry
  • Pyridazines / metabolism*
  • Receptors, Progesterone / metabolism*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Ligands
  • Progestins
  • Pyridazines
  • RWJ 25333
  • Receptors, Progesterone