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

Article Details

Citation

Combs DW, Reese K, Cornelius LA, Gunnet JW, Cryan EV, Granger KS, Jordan JJ, Demarest KT

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.

PubMed ID
8523400 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
NorethisteroneProgesterone receptorIC 50 (nM)3.2N/AN/ADetails
ProgesteroneProgesterone receptorIC 50 (nM)17N/AN/ADetails