Studies on Aromatase Inhibitors.I.Synthesis and Biological Evaluation of 4-Amino-4H-1,2,4-triazole Derivatives
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- OKADA Minoru
- Endocrinology/Metabolic Disease Laboratories
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- YODEN Toru
- Endocrinology/Metabolic Disease Laboratories
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- KAWAMINAMI Eiji
- Endocrinology/Metabolic Disease Laboratories
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- SHIMADA Yoshiaki
- Endocrinology/Metabolic Disease Laboratories
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- KUDOH Masafumi
- Endocrinology/Metabolic Disease Laboratories
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- ISOMURA Yasuo
- Infectious Disease/Immunology Research Laboratories
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- SHIKMA Hisataka
- Endocrinology/Metabolic Disease Laboratories
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- FUJIKURA Takashi
- Endocrinology/Metabolic Disease Laboratories
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抄録
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 IC_<50> values of 0.4 and 0.12 nM in in vitro experiments using rat ovary and human placenta, respectively, and an in vivo ED_<50>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.
収録刊行物
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- Chemical & pharmaceutical bulletin
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Chemical & pharmaceutical bulletin 44 (10), 1871-1879, 1996-10-15
公益社団法人日本薬学会
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詳細情報
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- CRID
- 1573950402116321408
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- NII論文ID
- 110003631779
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- NII書誌ID
- AA00602100
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- ISSN
- 00092363
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- 本文言語コード
- en
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- データソース種別
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- CiNii Articles