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

Abstract

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 (R a-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 16β-oriented. All compounds were tested as inhibitors of type 1 17β-HSD. The inhibitory potency increases in the following order 1 < 2 < 3, suggesting that the presence of a flexible 16β-methylene group allows a better positioning of the aryl moiety. With an IC50 of 0.8 μM, the 16β-benzyl-E2 (3a) is the best inhibitor in this series. © 2005 Elsevier Ireland Ltd. All rights reserved.