17-(2-phosphonatoethylidienyl)-3-methoxy-1,3,5(10)-estratriene

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 17-(2-phosphonatoethylidienyl)-3-methoxy-1,3,5(10)-estratriene
• 英文别名: 2-(3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ylidene)vinylphosphonic acid
• 化学式: C₂₁H₂₇O₄P
• 分子量: 374.417
• InChiKey: PYVQTASVCPATQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (17α)-3-methoxy-19-norpregna-1,3,5(10)-triene-20-yn-17-ol 、 三氯化磷 在 水 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 9.0h， 以61%的产率得到17-(2-phosphonatoethylidienyl)-3-methoxy-1,3,5(10)-estratriene
  参考文献：
  名称：

  Effects of steroidal allenic phosphonic acid derivatives on the parasitic protists Leishmania donovani, Leishmania mexicana mexicana, and Pneumocystis carinii carinii

  摘要：

  已知有几种致病真菌和原虫具有与其哺乳动物宿主不同的甾醇。作为药物开发的特别关注目标是重要寄生虫如鞭毛虫和艾滋病相关的机会主义原虫卡氏肺孢子菌的甾醇生物合成。这些病原体合成具有C-24烷基的甾醇，并且一些侧链上有C-22的双键。人类和其他哺乳动物宿主无法进行C-24烷基化和C-22去饱和。在本研究中，合成了三种侧链被膦酸酯基替代的甾体化合物，并对利什曼原虫和墨西哥利什曼原虫的培养生长产生影响进行了测试。这些化合物在微克/毫升浓度下抑制了生物体的增殖。这组化合物中最有效的抑制剂是在磷酸酯功能上具有两个乙基基团的化合物。利什曼原虫经过17-[2-(二乙基膦酸酯基)乙烯基] 3-甲氧基-19-去甲孕-1,3,5-三烯处理后，在无抑制剂的培养基中转移后生长减缓。由于目前没有连续亚培养卡氏肺孢子菌的无菌方法，因此通过两种替代筛选方法评估了这些药物对该病原体的影响。同样的两种二乙基膦酸酯甾体化合物不仅抑制了利什曼原虫的增殖，而且通过减少细胞ATP含量对卡氏肺孢子菌也有很强的作用。通过双重荧光染色活死检测，囊性和营养形态都对药物治疗产生了反应。甾体膦酸盐的其他修饰可能会导致开发出具有更高活性和对病原体具有更高特异性的相关药物。

  DOI：

  10.1128/aac.41.1.162

文献信息

• Effects of steroidal allenic phosphonic acid derivatives on the parasitic protists Leishmania donovani, Leishmania mexicana mexicana, and Pneumocystis carinii carinii
  作者：D H Beach、F Chen、M T Cushion、R S Macomber、G A Krudy、M A Wyder、E S Kaneshiro

  DOI：10.1128/aac.41.1.162

  日期：1997.1

  Several pathogenic fungi and protozoa are known to have sterols distinct from those of their mammalian hosts. Of particular interest as targets for drug development are the biosyntheses of the sterols of important parasites such as the kinetoplastid flagellates and the AIDS-associated opportunistic protist Pneumocystis carinii. These pathogens synthesize sterols with an alkyl group at C-24, and some have a double bond at C-22 of the side chain. Humans and other mammalian hosts are incapable of C-24 alkylation and C-22 desaturation. In the present study, three steroidal compounds with side chains substituted by phosphonyl-linked groups were synthesized and tested for their effects on Leishmania donovani and L. mexicana mexicana culture growth. The compounds inhibited organism proliferation at concentrations in micrograms per milliliter. The most potent inhibitors of this group of compounds were characterized by two ethyl groups at the phosphate function. Leishmania organisms treated with 17-[2-(diethylphosphonato) ethylidienyl]3-methoxy-19-norpregna-1,3,5-triene exhibited reduced growth after transfer into inhibitor-free medium. Because there are currently no axenic methods available for the continuous subcultivation of P. carinii, the effects of these drugs on this organism were evaluated by two alternative screening methods. The same two diethyl phosphonosteroid compounds that inhibited Leishmania proliferation were also the most active against P. carinii as determined by the potent effect they had on reducing cellular ATP content. Cystic as well as trophic forms responded to the drug treatments, as evaluated by a dual fluorescent staining live-dead assay. Other modifications of steroidal phosphonates may lead to the development of related drugs with increased activity and specificity for the pathogens.

  已知有几种致病真菌和原虫具有与其哺乳动物宿主不同的甾醇。作为药物开发的特别关注目标是重要寄生虫如鞭毛虫和艾滋病相关的机会主义原虫卡氏肺孢子菌的甾醇生物合成。这些病原体合成具有C-24烷基的甾醇，并且一些侧链上有C-22的双键。人类和其他哺乳动物宿主无法进行C-24烷基化和C-22去饱和。在本研究中，合成了三种侧链被膦酸酯基替代的甾体化合物，并对利什曼原虫和墨西哥利什曼原虫的培养生长产生影响进行了测试。这些化合物在微克/毫升浓度下抑制了生物体的增殖。这组化合物中最有效的抑制剂是在磷酸酯功能上具有两个乙基基团的化合物。利什曼原虫经过17-[2-(二乙基膦酸酯基)乙烯基] 3-甲氧基-19-去甲孕-1,3,5-三烯处理后，在无抑制剂的培养基中转移后生长减缓。由于目前没有连续亚培养卡氏肺孢子菌的无菌方法，因此通过两种替代筛选方法评估了这些药物对该病原体的影响。同样的两种二乙基膦酸酯甾体化合物不仅抑制了利什曼原虫的增殖，而且通过减少细胞ATP含量对卡氏肺孢子菌也有很强的作用。通过双重荧光染色活死检测，囊性和营养形态都对药物治疗产生了反应。甾体膦酸盐的其他修饰可能会导致开发出具有更高活性和对病原体具有更高特异性的相关药物。