Potent nonsteroidal progesterone receptor agonists: synthesis and SAR study of 6-aryl benzoxazines.

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Zhang P, Terefenko EA, Fensome A, Zhang Z, Zhu Y, Cohen J, Winneker R, Wrobel J, Yardley J

Potent nonsteroidal progesterone receptor agonists: synthesis and SAR study of 6-aryl benzoxazines.

Bioorg Med Chem Lett. 2002 Mar 11;12(5):787-90.

PubMed ID
11859003 [ View in PubMed
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Abstract

Novel 6-aryl benzoxazines were prepared and examined as progesterone receptor (PR) modulators. In contrast to the structurally related 6-aryl dihydroquinoline PR antagonists, the 6-aryl benzoxazines were potent PR agonists. Compounds 4e, 5b, and 6a with the 2,4,4-trimethyl-1,4-dihydro-2H-benzo[d][1,3]oxazine core were the most potent PR agonists in the series with sub-nanomolar activities (EC(50) 0.20-0.35nM). Compound 6a was more potent than progesterone (P4) in the in vivo decidualization assay in an ovariectomized female rat model by subcutaneous administration with an ED(50) of 1.5mg/kg (vs 5.62mg/kg for P4).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Medroxyprogesterone acetateProgesterone receptorEC 50 (nM)0.12N/AN/ADetails
Medroxyprogesterone acetateProgesterone receptorIC 50 (nM)11N/AN/ADetails
MifepristoneProgesterone receptorIC 50 (nM)0.2N/AN/ADetails
ProgesteroneProgesterone receptorEC 50 (nM)0.92N/AN/ADetails
ProgesteroneProgesterone receptorIC 50 (nM)3.5N/AN/ADetails