Novel 6-aryl-1,4-dihydrobenzo[d]oxazine-2-thiones as potent, selective, and orally active nonsteroidal progesterone receptor agonists.
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Zhang P, Terefenko EA, Fensome A, Wrobel J, Winneker R, Zhang Z
Novel 6-aryl-1,4-dihydrobenzo[d]oxazine-2-thiones as potent, selective, and orally active nonsteroidal progesterone receptor agonists.
Bioorg Med Chem Lett. 2003 Apr 7;13(7):1313-6.
- PubMed ID
- 12657271 [ View in PubMed]
- Abstract
The functional activity of 6-aryl benzoxazinone-based progesterone (PR) antagonists changed to PR agonism when the 2-carbonyl group was replaced by a 2-thiocarbonyl moiety. Based on this finding novel 6-aryl benzoxazine-2-thiones were synthesized and evaluated as PR agonists in various in vitro and in vivo assays. Several analogues had sub-nanomolar in vitro potency and showed excellent oral activities in rats. Compounds 15 and 29 had similar potencies to medroxyprogesterone acetate (MPA) in the in vitro T47D alkaline phosphatase assay and in vivo rat decidualization model. In contrast to MPA, 29 was highly selective (>500-fold) for PR over glucocorticoid and androgen receptors.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Medroxyprogesterone acetate Progesterone receptor EC 50 (nM) 0.12 N/A N/A Details Medroxyprogesterone acetate Progesterone receptor EC 50 (nM) 0.1 N/A N/A Details Medroxyprogesterone acetate Progesterone receptor IC 50 (nM) 10.8 N/A N/A Details Progesterone Glucocorticoid receptor IC 50 (nM) >1000 N/A N/A Details Progesterone Progesterone receptor EC 50 (nM) 0.92 N/A N/A Details Progesterone Progesterone receptor EC 50 (nM) 0.9 N/A N/A Details