Dw. Combs et al., NONSTEROIDAL PROGESTERONE-RECEPTOR LIGANDS .2. HIGH-AFFINITY LIGANDS WITH SELECTIVITY FOR BONE CELL PROGESTERONE RECEPTORS, Journal of medicinal chemistry, 38(25), 1995, pp. 4880-4884
A novel series of nonsteroidal heterocycles was discovered which displ
ay cell-type selective, high-affinity (nanomolar) binding to the proge
sterone receptors from TE85 osteosarcoma cells but >1 mu M binding aff
inity to the progesterone receptors from T47D and ZR75 human breast ca
rcinoma cells. Structure-activity relationships were developed for a s
et of these compounds, and a representative analog lorobenzoyl)-3-phen
yl-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.