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

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 3 beta-hydroxy-21-hydroxymethylidenepregn-5-en-3 beta-ol-20-one (5) with phenylhydrazine in the synthesis of pyrazolyl derivatives. Compounds of both the series were tested for their 5 alpha-reductase inhibitory activities. Amongst all the compounds screened for their 5 alpha-reductase inhibitory activities, compound 4b, 4c and 6b were found to be the most active. (C) 2014 Elsevier Inc. All rights reserved.