title: Studies on aromatase inhibitors. II. Synthesis and biological evaluation of 1-amino-1H-1,2,4-triazole derivatives.
abstract: 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.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Yoden
authors.forename: E
authors.initials: E
authors.lastname: Kawaminami
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.forename: M
authors.initials: M
authors.lastname: Kudoh
authors.forename: Y
authors.initials: Y
authors.lastname: Isomura
mesh_terms: 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
chemical_list: D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D006064:Gonadotropins, Equine; D014230:Triazoles; D000450:Aldosterone