Synthesis and effect of terminating early pregnancy of progesterone receptor antagonist mifepristone derivatives

Aim To search for novel progesterone receptor antagonist with higher efficiency and less antiglucocorticoid effects.Methods The structure of progesterone receptor antagonist mifepristone at C_ 11,C_ 13,C_ 17-substitute were modified.Seven mifepristone derivatives were synthesized from 3-ketal-5(10),9(11)-estradiene-17-one through epoxidation,the addition of aromatic Grignard agent,addition,reduction and hydrolysis.All of them have not been reported in literature previously.Their structures were confirmed by IR, 1H-NMR and MS spectra.Result All the compound showed similar or lower antagonistic effect on progesterone receptor.The antiprogesterone effect of compound 9d was similar to mifepristone with less antiglucocorticoid effects.Conclusion Introduction of bigger group at C_ 11 will not alter the antiprogesterone effect,while introduction of polar group at C_ 17 may induce less antiglucocorticoid effects.