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

Starting from 3β-acetoxy-15-cyano-17-oxo-16,17-seco-5-androstene (2) and 3β-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. Compounds5–10, 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.