Synthesis, 17α-hydroxylase-C17,20-lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives

Abstract

A series of 1,5-diaryl pyrazoline pregnenolones were synthesized and screened for 5α-reductase inhibitory activities. Synthesis of the analogs is multistep and proceeds in good overall yields. The key step in the synthesis of 1,5-disubstituted pyrazolinyl pregnenolones (5a-l) is the heterocyclization of bezylidine derivatives (3) in presence of phenylhydrazines (4) through the initial formation of the phenylhydrazones, which undergo concomitant cyclization to generate the stable pyrazoline derivatives. All compounds were tested for their prostate cancer cell inhibitory, 5α-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activities. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active. Further, compounds 5g and 5h were found to have moderate 17α-hydroxylase-C17,20-lyase inhibitory activities.