6-Aryl-1,4-dihydro-benzo[d][1,3]oxazin- 2-ones: a novel class of potent, selective, and orally active nonsteroidal progesterone receptor antagonists.

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Zhang P, Terefenko EA, Fensome A, Wrobel J, Winneker R, Lundeen S, Marschke KB, Zhang Z

6-Aryl-1,4-dihydro-benzo[d][1,3]oxazin- 2-ones: a novel class of potent, selective, and orally active nonsteroidal progesterone receptor antagonists.

J Med Chem. 2002 Sep 26;45(20):4379-82.

PubMed ID

12238914 [ View in PubMed

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Abstract

Novel 6-aryl-1,4-dihydro-benzo[d][1,3]oxazin-2-ones were synthesized and tested as progesterone receptor (PR) antagonists. These compounds were potent and showed good selectivity for PR over other steroid receptors such as the glucocorticoid and androgen receptors (e.g., greater than 80-fold selectivity at PR for 4h). Numerous 6-aryl benzoxazinones (e.g., 4h-j) were active orally in the uterine decidualization and component C3 assays in the rats. In these in vivo models,4h had potencies comparable to mifepristone.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mifepristone	Glucocorticoid receptor	IC 50 (nM)	0.8	N/A	N/A	Details
Mifepristone	Progesterone receptor	IC 50 (nM)	0.3	N/A	N/A	Details
Mifepristone	Progesterone receptor	IC 50 (nM)	0.13	N/A	N/A	Details