tetraethyl (((2,3-dihydro-1H-inden-5-yl)amino) methylene)bis(phosphonate)

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: tetraethyl (((2,3-dihydro-1H-inden-5-yl)amino) methylene)bis(phosphonate)
• 英文别名: N-[bis[diethoxy(oxido)phosphaniumyl]methyl]-2,3-dihydro-1H-inden-5-amine
• 化学式: C₁₈H₃₁NO₆P₂
• 分子量: 419.395
• InChiKey: ZJMIGKHCKUMOHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tetraethyl (((2,3-dihydro-1H-inden-5-yl)amino) methylene)bis(phosphonate) 在 盐酸 作用下， 生成 [(5-indanyl)aminomethylene]-1,1-bisphosphonate
  参考文献：
  名称：

  Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

  摘要：

  The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 < 200 muM) versus E. histolytica growth in vitro. The most active compounds (IC50 similar to 4-9 muM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 similar to 10-20 muM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK(a) values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values <200 muM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC50 values around 1 muM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.

  DOI：

  10.1021/jm030084x
• 作为产物：
  描述：

  5-氨基茚旦 、 原甲酸三乙酯 、 亚磷酸二乙酯 在 di-n-butyl ammonium chlorosulfonate 作用下， 反应 0.33h， 以92%的产率得到tetraethyl (((2,3-dihydro-1H-inden-5-yl)amino) methylene)bis(phosphonate)
  参考文献：
  名称：

  Di-n-butyl ammonium chlorosulfonate as a highly efficient and recyclable ionic liquid for the synthesis of N-containing bisphosphonates

  摘要：

  The preparation and description of a novel secondary amine ionic liquid, di-n-butyl ammonium chlorosulfonate, is described. The di-n-butyl ammonium ionic liquid (DBA IL) was characterized by FT-IR, elemental analysis, NMR spectroscopies, and wide-angle X-ray scattering techniques, as well as thermogravimetric analysis. The DBA IL functions as an efficient, environmentally benign, and recyclable catalyst with short reaction times and high catalytic activity for the synthesis of a variety of N-containing bisphosphonates in high yields. Another merit of this ionic liquid shown that the purification of products by non-chromatographic method with good to excellent yields of the desired products. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.catcom.2014.12.021

文献信息

• Effects of Bisphosphonates on the Growth of <i>Entamoeba histolytica</i> and <i>Plasmodium </i>Species in Vitro and in Vivo
  作者：Subhash Ghosh、Julian M. W. Chan、Christopher R. Lea、Gary A. Meints、Jared C. Lewis、Zev S. Tovian、Ryan M. Flessner、Timothy C. Loftus、Iris Bruchhaus、Howard Kendrick、Simon L. Croft、Robert G. Kemp、Seiki Kobayashi、Tomoyoshi Nozaki、Eric Oldfield

  DOI：10.1021/jm030084x

  日期：2004.1.1

  The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 < 200 muM) versus E. histolytica growth in vitro. The most active compounds (IC50 similar to 4-9 muM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 similar to 10-20 muM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK(a) values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values <200 muM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC50 values around 1 muM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.
• Synthesis and Evaluation of Effective Inhibitors of Plant δ¹-Pyrroline-5-carboxylate Reductase
  作者：Giuseppe Forlani、Łukasz Berlicki、Mattia Duò、Gabriela Dziędzioła、Samuele Giberti、Michele Bertazzini、Paweł Kafarski

  DOI：10.1021/jf401234s

  日期：2013.7.17

  Analogues of previously studied phenyl-substituted aminomethylene-bisphosphonic acids were synthesized and evaluated as inhibitors of Arabidopsis thaliana delta(1)-pyrroline-5-carboxylate reductase. With the aim of improving their effectiveness, two main modifications were introduced into the inhibitory scaffold: the aminomethylenebisphosphonic moiety was replaced with a hydroxymethylenebisphosphonic group, and the length of the molecule was increased by replacing the methylene linker with an ethylidene chain. In addition, chlorine atoms in the phenyl ring were replaced with various other substituents. Most of the studied derivatives showed activity in the rnicromolar to millimolar range, with two of them being more effective than the lead compound, with concentrations inhibiting 50% of enzyme activity as low as 50 mu M. Experimental evidence supporting the ability of these inhibitors to interfere with proline synthesis in vivo is also shown.
• Di-n-butyl ammonium chlorosulfonate as a highly efficient and recyclable ionic liquid for the synthesis of N-containing bisphosphonates
  作者：MudumalaVeeranarayana Reddy、Reddi Mohan Naidu Kalla、Lee Sang Dong、Yeon Tae Jeong

  DOI：10.1016/j.catcom.2014.12.021

  日期：2015.2

  The preparation and description of a novel secondary amine ionic liquid, di-n-butyl ammonium chlorosulfonate, is described. The di-n-butyl ammonium ionic liquid (DBA IL) was characterized by FT-IR, elemental analysis, NMR spectroscopies, and wide-angle X-ray scattering techniques, as well as thermogravimetric analysis. The DBA IL functions as an efficient, environmentally benign, and recyclable catalyst with short reaction times and high catalytic activity for the synthesis of a variety of N-containing bisphosphonates in high yields. Another merit of this ionic liquid shown that the purification of products by non-chromatographic method with good to excellent yields of the desired products. (C) 2014 Elsevier B.V. All rights reserved.