Synthesis of 11 beta-(4-dimethylaminophenyl)-17 beta-hydroxy-17 alpha-(3-methyl-1-butynyl)-4, 9-estradien-3-one and 11 beta-(4-acetophenyl)-17 beta-hydroxy-17 alpha-(3-methyl-1-butynyl)-4, 9-estradien-3-one: two new analogs of mifepristone (RU-486)

From the structure activity relationship, two new analogs, 2 and 3, of the potent progesterone antagonist mifepristone 1 have been designed. The synth eses of these two analogs have been achieved in eleven steps through modifi ed synthetic sequences and improved procedures starting from (+)-estrone. I n comparison with mifepristone 1, the relative binding affinities of compou nd 2 for the progesterone receptor was found to be more, whereas that of co mpound 3 was less. (C) 2000 Elsevier Science Inc. All rights reserved.