Vinyl fluoride as a mimic of the 'intermediate' enol form in the 5α-reductase transformation: Synthesis and in vitro activity of (N-1′,1′-dimethylethyl)-3-haloandrost-3,5-diene-17β- carboxamides

Article abstract of DOI:10.1016/0968-0896(95)00160-3

(N-1′,1′-Dimethylethyl)-3-haloandrost-3,5-diene-17ss- carboxamides (9-11) and the methyl ester 8 were prepared from 3-chloro/bromoandrost-3,5-diene-17β-carboxylic chloride/bromide (6/7), which were obtained from pregnenolone. In comparison with finasteride and 4-MA, compounds 8-11 showed very weak inhibitory activity (≤10% inhibition) on human type I 5 α-reductase (transfected 293 cells) at 100 and 1000 nM concentrations. Against the type II enzyme, chloro compounds 8 and 9, and bromo 10 had no effect at 100 nM concentration, however, they were weak inhibitors of the type II (6.0% < inhibition < 30%) at a higher concentration. The best activity (IC₅₀ = 480 nM) was observed with the 3-vinyl fluoride analogue 11.