Steroidal pyrazolines and pyrazoles as potential 5α-reductase inhibitors: Synthesis and biological evaluation

•New 17β-steroidal pyrazolinyl and pyrazolyl derivatives synthesized.•All compounds were screened for their 5α-reductase inhibitory activity.•Most of the compounds showed better activity than Finasteride.•The compounds were selective towards type-I 5α-reductase.•Results provide new insights into steroid bioactivity/pharmacology.

Taking pregnenolone as the starting material, two series of pyrazolinyl and pyrazolyl pregnenolones were synthesized through different routes. The synthesis of the analogs of both series is multistep and proceeds in good overall yields. While the key step in the synthesis of pyrazolinyl pregnenolones is the heterocyclization of benzylidine derivatives (3) in presence of hydrazine hydrate, it is the condensation of 3β-hydroxy-21-hydroxymethylidenepregn-5-en-3β-ol-20-one (5) with phenylhydrazine in the synthesis of pyrazolyl derivatives. Compounds of both the series were tested for their 5α-reductase inhibitory activities. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 4b, 4c and 6b were found to be the most active.

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