Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-Diene or 4,6-Diene 20-Ones and 4-Azasteroid 20-Oximes

The study synthesized and evaluated various C21 steroids, including 4-azasteroids and epoxy derivatives, for their 5α-reductase inhibitory activity as potential alternatives to finasteride. Certain 20-oxime analogues showed potent inhibition, particularly when a lipophilic group was present at C-17, while hydrophilic epoxy groups generally decreased activity. Compounds like 3β-acetoxypregnenolone were ineffective, highlighting the necessity of a carbonyl group at C-3. The 20-oxime analogue of progesterone was less active than its carbonyl counterpart, and additional double bonds or epoxy groups reduced activity. Overall, while none surpassed finasteride, some structural features enhanced inhibitory potential.