Studies on Aromatase Inhibitors. II. Synthesis and Biological Evaluation of 1-Amino-1H-1, 2, 4-triazole Derivatives

1-N, N-Disubstituted amino-1H-1, 2, 4-triazole derivatives were prepared and evaluated for aromatase-inhibitory activity (in vitro) and for the inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). 1-N-para-Substituted benzylamino derivatives, having an electron-withdrawing group on the phenyl moiety, exhibited aromatase-inhibitory activity in vitro and in vivo. Among them, -[(4-nitrobenzyl)(4-nitrophenyl)amino]-1H-1, 2, 4-triazole (5b) was the most potent aromatase inhibitor. These 1-N-benzylamino derivatives also showed relatively strong inhibitory activity on aldosterone synthesis, indicating that the selectivity of these derivatives for aromatase inhibition was not sufficient in comparison with that of the 4-amino-4H-1, 2, 4-triazole derivatives.