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

• Published in: Chemical & pharmaceutical bulletin Vol. 45; no. 2; pp. 333 - 337
• Main Authors: OKADA, Minoru, YODEN, Toru, KAWAMINAMI, Eiji, SHIMADA, Yoshiaki, KUDOH, Masafumi, ISOMURA, Yasuo
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1997; Maruzen; Japan Science and Technology Agency
• Subjects: 1-amino-1H-1, 2, 4-triazole; aldosterone; Aldosterone - biosynthesis; Animals; Antineoplastic agents; aromatase; Aromatase Inhibitors; Biological and medical sciences; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; estrogen; Estrogens - biosynthesis; Female; General aspects; Gonadotropins, Equine - pharmacology; Medical sciences; Pharmacology. Drug treatments; Pregnancy; Rats; Rats, Wistar; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Nitro compound; Rat; Enzyme; Nitrogen heterocycle; Isozyme; Cytochrome P450; Rodentia; Enzyme inhibitor; Estrogen synthase; Aldosterone; In vitro; In vivo; Vertebrata; Mammalia; Structure activity relation; Animal; Triazole derivatives; Benzenic compound; Inhibition; Chemical synthesis
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.45.333

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.