Tegley C M, Zhi L, Marschke K B, Gottardis M M, Yang Q, Jones T K
Department of Medicinal Chemistry, New Leads Discovery, and Endocrine Research, Ligand Pharmaceuticals, Inc., 10275 Science Center Drive, San Diego, California 92121, USA.
J Med Chem. 1998 Oct 22;41(22):4354-9. doi: 10.1021/jm980366a.
A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-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 assay with high efficacy (132% and 166%) and binding affinity (Ki = 0.66 and 0.83 nM) similar to medroxyprogesterone acetate (MPA) (Ki = 0.34 nM). A representative analogue, 8, demonstrated similar oral potency to MPA in the uterine wet weight/mammary gland morphology assay in ovariectomized rats.
