5-BENZYLIDENE 1,2-DIHYDROCHROMENO[3,4-F]QUINOLINES, A NOVEL CLASS OF NONSTEROIDAL HUMAN PROGESTERONE-RECEPTOR AGONISTS

A novel series of nonsteroidal progestins, 5-benzylidene-1,2-dihydroch romeno[3,4-f]quinolines (2), was discovered, and a preliminary structu re-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16) . These new progestins showed biological activities (EC50 = 5.7 and 7. 6 nM) similar to progesterone (EC50 = 2.9 nM) in the cotransfection as say with high efficacy (132% and 166%) and binding affinity (K-i = 0.6 6 and 0.83 nM) similar to medroxyprogesterone acetate (MPA) (K-i = 0.3 4 nM). A representative analogue, 8, demonstrated similar oral potency to MPA in the uterine wet weight/mammary gland morphology assay in ov ariectomized rats.