Studies on aromatase inhibitors. II. Synthesis and biological evaluation of 1-amino-1H-1,2,4-triazole derivatives.
1-N,N-Disubstituted amino-1-H-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, 1-[(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.
Okada
M
M
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Yoden
T
T
Kawaminami
E
E
Shimada
Y
Y
Kudoh
M
M
Isomura
Y
Y
D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D006064:Gonadotropins, Equine; D014230:Triazoles; D000450:Aldosterone