Author/Authors :
Puwen Zhang، نويسنده , , Eugene A. Terefenko، نويسنده , , Andrew Fensome، نويسنده , , Zhiming Zhang، نويسنده , , Yuan Zhu، نويسنده , , Jeffrey Cohen، نويسنده , , Richard Winneker، نويسنده , , Jay Wrobel، نويسنده , , John Yardley، نويسنده ,
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 (EC50 0.20–0.35 nM). 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 ED50 of 1.5 mg/kg (vs 5.62 mg/kg for P4).
