Patent Evaluation: Δ-4,6-Steroids as Potent 5α-Reductase Inhibitors

In 1992, Merrell Dow Pharmaceuticals Inc. patented a new series of Δ-4,6-steroids as potent inhibitors of the enzyme 5α-reductase, which are disclosed in patent EP-469547-A. These compounds, particularly 4-amino-N,N-bis-(1-methylethyl)-3-oxoandrosta-4,6-diene-17ß-carboxamide, showed promise for the treatment of conditions such as acne, androgenic alopecia, seborrhea, hypertrophy, female hirsutism, and benign prostatic cancer. The most potent compound in this series demonstrated an in vitro inhibition with an IC50 value of 8nM, indicating a high level of effectiveness. The synthesis of these compounds involved a straightforward chemical process. The Δ-4,6-steroids were found to be more potent than the previously disclosed Δ-4-steroids, with the Δ-4,6-steroid having an IC50 of 8nM compared to the Δ-4-steroid's IC50 of 59nM. This patent represented a new subclass of 5α-reductase inhibitors and indicated Merrell Dow's commitment to developing treatments in this area, distinguishing their work from other major industry players like Merck and SmithKline Beecham.