BIOMAT Database Logo BIOMAT Database Logo

Studies on aromatase inhibitors. I. Synthesis and biological evaluation of 4-amino-4H-1,2,4-triazole derivatives. 1996

M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
Endocrinology/Metabolic Disease Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tsukuha, Japan.

Various 4-N-substituted amino-4H-1,2,4-triazole derivatives were synthesized and evaluated for aromatase-inhibitory activity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis-inhibitory activity (in vivo). The 4-(4-cyanophenyl) amino derivative and 4-(4-nitrophenyl)amino derivative, each possessing a strong electron-withdrawing group on the phenyl moiety, showed potent aromatase-inhibitory activity. Structure-activity relationship studies indicated that 4-[(4-bromobenzyl)(4-cyanophenyl)amino]-4H-1,2,4-triazole (5k, YM511) is a highly potent aromatase inhibitor with IC50 values of 0.4 and 0.12 nM in in vitro experiments using rat ovary and human placenta, respectively, and an in vivo ED50 of 0.002 mg/kg in rats on oral administration. YM511 was also a weak inhibitor of other steroid hormone synthesis enzymes. These data suggest that YM511 is a highly selective aromatase inhibitor and may be a useful agent for the treatment of estrogen-dependent diseases such as breast cancer.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002627 Chemistry, Physical The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes. Physical Chemistry,Chemistries, Physical,Physical Chemistries
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004967 Estrogens Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D005260 Female Females
D006064 Gonadotropins, Equine Gonadotropins secreted by the pituitary or the placenta in horses. This term generally refers to the gonadotropins found in the pregnant mare serum, a rich source of equine CHORIONIC GONADOTROPIN; LUTEINIZING HORMONE; and FOLLICLE STIMULATING HORMONE. Unlike that in humans, the equine LUTEINIZING HORMONE, BETA SUBUNIT is identical to the equine choronic gonadotropin, beta. Equine gonadotropins prepared from pregnant mare serum are used in reproductive studies. Pregnant Mare Serum Gonadotropins,PMS Gonadotropins,PMSG (Gonadotropins),Equine Gonadotropins,Gonadotropins, PMS
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

Related Publications

M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
Synthesis and aromatase inhibitory evaluation of 4-N-nitrophenyl substituted amino-4H-1,2,4-triazole derivatives.
October 2016, Bioorganic & medicinal chemistry,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
Design, synthesis and biological evaluation of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives.
August 2016, Bioorganic & medicinal chemistry letters,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
Design, synthesis and biological evaluation of glycolamide, glycinamide, and β-amino carbonyl 1,2,4-triazole derivatives as DPP-4 inhibitors.
September 2021, Bioorganic chemistry,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
4-Amino-3,5-dimethyl-4H-1,2,4-triazole.
May 2008, Acta crystallographica. Section E, Structure reports online,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
4-[4-(Diethyl-amino)benzyl-ideneamino]-4H-1,2,4-triazole.
May 2008, Acta crystallographica. Section E, Structure reports online,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
5-Amino-3-(4H-1,2,4-triazol-4-yl)-1H-1,2,4-triazole.
September 2012, Acta crystallographica. Section E, Structure reports online,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
Synthesis and biological evaluation of 3-amino-1,2,4-triazole derivatives as potential anticancer compounds.
November 2020, Bioorganic chemistry,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
Synthesis and biological evaluation of (4H-1,2,4-triazol-4-yl)isoquinoline derivatives as selective glycine transporter 1 inhibitors.
January 2012, Bioorganic & medicinal chemistry,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
4-Amino-3,5-di-2-pyridyl-4H-1,2,4-triazole.
August 2008, Acta crystallographica. Section E, Structure reports online,
M Okada, and T Yoden, and E Kawaminami, and Y Shimada, and M Kudoh, and Y Isomura, and H Shikama, and T Fujikura
4-Amino-3-(4-pyrid-yl)-1,2,4-triazole-5(4H)-thione.
December 2007, Acta crystallographica. Section E, Structure reports online,
Copied contents to your clipboard!