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

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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.

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詳細情報

  • CRID
    1573950402116321408
  • NII論文ID
    110003631779
  • NII書誌ID
    AA00602100
  • ISSN
    00092363
  • 本文言語コード
    en
  • データソース種別
    • CiNii Articles

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