Synthesis and in vitro antiandrogenic activity of 17β-hydroxy-17α-(ω-hydroxy/haloalkyn-1′-yl)-4-methyl-4-aza-3-oxo-5α-androstan-(1-ene)-3-ones

Synthesis of 17β-hydroxy-17α-(ω-hydroxy/haloalkyn-1′-yl)-4-methyl-4-aza-(1-ene)-5α-steroids (7–22) was achieved by the addition of THP protected hydroxy alkynyllithium to 4-methyl-4-aza-(1-ene)-5α-androstan-3,17-diones (1 and 2), followed by deprotection and halogenation of 17α-(ω-hydroxy) compounds (7–10). Chloro- compounds 13 and 14, and iodo- compound 21 are potent antiandrogens. Introduction of a 1,2-double bond increased the potency by 2-fold compared to the parent compounds.