Synthesis, crystal structure and antiaromatase activity of 17-halo-16,17-seco-5-androstene derivatives

Abstract

Starting from 3b-acetoxy-15-cyano-17-oxo-16,17-seco-5-androstene (2) and 3b-acetoxy-15-cyano-17-hydroxy-17-methyl-16,17-seco-5-androstene (11), new 17-halo-derivatives (5–10 and 13) were obtained. The fluoro derivative 5 was obtained from 17-tosylate 4 in reaction with tetrabutylammonium fluoride. The structure of the 17-iodo-devitive 10 was unambiguously proved by the appropriate X-ray structural analysis. Compounds 5–10, as well as 12 and 13, were tested for possible anti-aromatase activity, whereby only compound 9, with bromine as the C-17 substituent, induced 19.4 % inhibition of aromatase activity compared to the control.

Keywords

• 17-halo derivatives of 5-androstene
• D-seco-steroids
• aromatase inhibitors