MR 20814

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: MR 20814
• 英文别名: 3-Amino-5-methoxy-2-(pyridin-4-ylmethyl)inden-1-one
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: LADVDHPMHRSARD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-吡啶甲醛 、 2,2,2-trifluoro-N-(6-methoxy-3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以56%的产率得到MR 20814
  参考文献：
  名称：

  Evidence for new non-steroidal human aromatase inhibitors and comparison with equine aromatase inhibition for an understanding of the mammalian active site

  摘要：

  We developed a new comparative model in order to better understand the structure-function relationships of the active site in human aromatase. Thus, we undertook the comparative inhibition of human and equine aromatases with new compounds. In fact, equine aromatase represents the only easy and available mammalian membrane-bound enzyme model, besides the human one, which is biochemically purified, well characterized and cloned. During the course of our work concerning the synthesis and screening of new drugs on human and equine aromatases, we identified two new indane derivatives which inhibited the human enzyme (IC50 = 3.5 mu M and 5.9 mu M) strongly and selectively while they were much less active on the equine one (IC50 > 10 mu M). The hitherto known aromatase inhibitors, such as 4-hydroxyandrostenedione (4-OHA) and some other indane-related derivatives, are equally efficient on both human and equine enzymes. In this work, using a theoretical 3D model of aromatase, we have explained the human selectivity of the new described compounds as due to the specific differences between the primary structure of both active sites in human and equine enzymes. These results could allow synthesis of a new family of compounds that are much more potent and selective aromatase inhibitors. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80046-9

文献信息

• Evidence for new non-steroidal human aromatase inhibitors and comparison with equine aromatase inhibition for an understanding of the mammalian active site
  作者：Pierrick Auvray、Safa Moslemi、Pascal Sourdaine、Sébastien Galopin、Gilles-Eric Séralini、Cécile Enguehard、Patrick Dallemagne、Ronan Bureau、Pascal Sonnet、Sylvain Rault

  DOI：10.1016/s0223-5234(98)80046-9

  日期：1998.6

  We developed a new comparative model in order to better understand the structure-function relationships of the active site in human aromatase. Thus, we undertook the comparative inhibition of human and equine aromatases with new compounds. In fact, equine aromatase represents the only easy and available mammalian membrane-bound enzyme model, besides the human one, which is biochemically purified, well characterized and cloned. During the course of our work concerning the synthesis and screening of new drugs on human and equine aromatases, we identified two new indane derivatives which inhibited the human enzyme (IC50 = 3.5 mu M and 5.9 mu M) strongly and selectively while they were much less active on the equine one (IC50 > 10 mu M). The hitherto known aromatase inhibitors, such as 4-hydroxyandrostenedione (4-OHA) and some other indane-related derivatives, are equally efficient on both human and equine enzymes. In this work, using a theoretical 3D model of aromatase, we have explained the human selectivity of the new described compounds as due to the specific differences between the primary structure of both active sites in human and equine enzymes. These results could allow synthesis of a new family of compounds that are much more potent and selective aromatase inhibitors. (C) Elsevier, Paris.