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

Abstract 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.