Nonsteroidal Progesterone Receptor Ligands. 2. High-Affinity Ligands with Selectivity for Bone Cell Progesterone Receptors

Article abstract of DOI:10.1021/jm00025a004

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 μM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinpma 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.