Synthesis of some novel androstanes as potential aromatase inhibitors

Novel pyrazole and isoxazole derivatives (6–9) were synthesized as a aromatase inhibitors. Pyrazole was synthesized from hydrazine hydrate and isoxazoles from hydroxylamine hydrochloride under different conditions. Molecular docking studies were carried out for the synthesized compounds. The best score was obtained for the compound (9) followed by compound (6) while compound (8) afforded poorest of the score. Aromatase inhibitory activity for compound (6) having pyrazole ring at 2,3 position showed highest activity followed by nitrile derivative (9). Isomeric forms of isoxazole (7 and 8) showed very poor activity compared to fadrozole and aminoglutethimide. Preliminary kinetic studies have shown that both of the active compounds (6 and 9) are reversible inhibitors of the enzyme.

Figure optionsDownload as PowerPoint slideResearch highlights▶ The novel pyrazole (6), isoxazole (7 and 8) and nitrile (9) derivatives were synthesized. ▶ Aromatase inhibitory activity for compound (6) having pyrazole ring at 2,3 position showed the highest activity followed by nitrile derivative (9). ▶ Both of these compounds (6 and 9) bear a hydrogen bond donating group at position 3 of the A-ring. ▶ Preliminary kinetic studies have shown that both of the active compounds (6 and 9) are reversible inhibitors of the enzyme.