Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors.

Abstract In the present study, a series of steroidal tetrazole derivatives of androstane and pregnane have been prepared in which the tetrazole moiety was appended at C-3 and 17a-aza locations. 3-Tetrazolo-3,5-androstadien-17-one ( 6 ), 3-tetrazolo-19-nor-3,5-androstadien-17-one ( 10 ), 3-tetrazolo-3,5-pregnadien-20-one ( 14 ), 17a-substituted 3-tetrazolo-17a-aza- d -homo-3,5-androstadien-17-one ( 26 – 31 ) and 3-(2-acetyltetrazolo)-17a-aza- d -homo-3,5-androstadien-17-one ( 32 ) were synthesized from dehydroepiandrosterone acetate (1) through multiple synthetic steps. Some of the synthesized compounds were evaluated for their in vitro 5α-reductase (5AR) inhibitory activity by measuring the conversion of [ 3 H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity also showed a significant reduction ( p 14 showed 5AR-2 inhibition with IC 50 being 15.6 nM as compared to clinically used drug finasteride (40 nM). There was also a significant inhibition of 5AR-1 with IC 50 547 nM compared to finasteride (453 nM).