Estrone and estradiol C-16 derivatives as inhibitors of type 1 17β-hydroxysteroid dehydrogenase

Three series of steroid derivatives, enones 1, enols 2 and saturated alcohols 3, were easily synthesized from estrone according to a sequence of three reactions: an aldol condensation with an aromatic aldehyde (Ra-gCHO) to afford 1, the carbonyl reduction of 1 to obtain the enol 2, and the double bond reduction of 2 to give 3 with the Ra-g group 16 beta-oriented. All compounds were tested as inhibitors of type 117 beta-HSD. The inhibitory potency increases in the following order 1 < 2 < 3, suggesting that the presence of a flexible 16 beta-methylene group allows a better positioning of the aryl moiety. With an IC50 of 0.8 mu M, the 16 beta-benzyl-E-2 (3a) is the best inhibitor in this series. (c) 2005 Elsevier Ireland Ltd. All rights reserved.