[2-(phenylamino)ethane-1,1-diyl]bis(phosphonic acid) | 204984-04-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: [2-(phenylamino)ethane-1,1-diyl]bis(phosphonic acid)
• 英文别名: phenylamino-2-ethylidene-1,1-bisphosphonic acid；N-phenylaminoethylidenebisphosphonic acid；β-(phenylamino)ethyl-α,α-bisphosphonic acid；(2-anilino-1-phosphono-ethyl)phosphonic Acid；(2-anilino-1-phosphonoethyl)phosphonic acid
• CAS: 204984-04-3
• 化学式: C₈H₁₃NO₆P₂
• 分子量: 281.142
• InChiKey: FPDLBFDOXAQQPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [2-(phenylamino)ethane-1,1-diyl]bis(phosphonic acid) 在 碘 、 碳酸氢钠 、 sodium sulfite 作用下， 以78%的产率得到((4-iodophenyl)amino)-2-ethylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  双膦酸酯衍生物抑制HIV-1整合酶的特征

  摘要：

  病毒DNA整合到细胞基因组中是1型人类免疫缺陷病毒（HIV-1）复制周期中的关键步骤之一。因此，催化该过程的病毒酶整合酶（IN）作为新型抗病毒剂的靶标引起了极大的兴趣。我们对五个不同系列的亚甲基双膦酸酯（BPs），PO 3 H 2 –C（R）（X）–PO 3 H 2进行了结构-功能分析。，作为IN抑制剂，旨在评估抑制活性所需的结构元素。我们发现IN仅受BP在P–C–P主链的桥碳上带有一个氯苄基取代基R的抑制。这些BP以相似的效率抑制了两种IN催化的反应。它们还对某些具有突变的IN起作用，这些突变具有针对抗链转移抑制剂的HIV-1菌株的特征性突变。对各种BP抑制IN的机理的研究表明，它受桥碳上第二个取代基（X）的影响。在测试的化合物中，只有氨基直接结合到BP桥碳上的BP被认为是非竞争性抑制剂，因此，作为整合前复合物中IN活性的潜在抑制剂，它有可能被进一步研究。

  DOI：

  10.1016/j.ejmech.2013.11.028
• 作为产物：
  描述：

  在 水 作用下， 反应 4.0h， 生成 [2-(phenylamino)ethane-1,1-diyl]bis(phosphonic acid)
  参考文献：
  名称：

  Low toxicity and unprecedented anti-osteoclast activity of a simple sulfur-containing gem-bisphosphonate: A comparative study

  摘要：

  Bisphosphonates (BPs) are key drugs for the treatment of bone resorption diseases like osteoporosis, Paget's disease and some forms of tumors. Recent findings underlined the importance of lipophilic N-containing BPs to ensure high biological activity. Herein we present some unprecedented results concerning the low toxicity and good anti-osteoclast activity of low molecular weight hydrophilic S-containing BPs. A series of S and N-containing BPs bearing aromatic and aliphatic substitution were prepared through Michael addition reaction between vinylidenebisphosphonate tetraethyl ester and the proper nucleophile under basic catalysis. S-containing BPs showed a generally low toxicity, determined with the neutral-red assay using the L929 cell line, and, in particular for an aliphatic one, a good biological activity assessed on primary cultures of human osteoclasts. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.032

文献信息

• Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity
  作者：D.V. Yanvarev、A.N. Korovina、N.N. Usanov、O.A. Khomich、J. Vepsäläinen、E. Puljula、M.K. Kukhanova、S.N. Kochetkov

  DOI：10.1016/j.biochi.2016.05.012

  日期：2016.8

  inhibitors of the phosphorolytic activity of native and drug-resistant forms of HIV-1 reverse transcriptase (RT) was performed. It was shown that with the increase of the inhibitory potential of BPs towards the phosphorolytic activity raises their ability to inhibit the RT-catalyzed DNA elongation. Herein, we report the impact of the thymidine analog mutations (TAM) on the activity of bisphosphonates, as well

  进行了36种亚甲基双膦酸酯（BPs）作为天然和耐药形式的HIV-1逆转录酶（RT）的磷酸水解抑制剂的结构功能分析。结果表明，随着BPs对磷酸分解活性的抑制潜能的增加，其抑制RT催化的DNA延伸的能力也随之增强。在本文中，我们报道了胸苷类似物突变（TAM）对双膦酸盐的活性以及BPs的某些结构特征的影响，从而使它们能够维持对核苷类似物治疗具有抗性的酶的抑制活性。我们估计了Mg（2 +）-配位基团结构，连接基和芳香族药效团对BPs抑制潜能的影响。根据31个BP SAR，
• Bisphosphonic acids as effective inhibitors of<i>Mycobacterium tuberculosis</i>glutamine synthetase
  作者：Paulina Kosikowska、Marta Bochno、Katarzyna Macegoniuk、Giuseppe Forlani、Paweł Kafarski、Łukasz Berlicki

  DOI：10.3109/14756366.2015.1070846

  日期：2016.11.1

  Inhibition of glutamine synthetase (GS) is one of the most promising strategies for the discovery of novel drugs against tuberculosis. Forty-three bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, were screened against recombinant GS from Mycobacterium tuberculosis. Most of the studied compounds exhibited activities in micromolar range, with N-(3,5-dichlorophenyl)-2-aminoethylidenebisphoshonic acid, N-(3,5difluorophenyl)-2-aminoethylidene-bisphoshonic acid and N-(3,4-dichlorophenyl)-1-hydroxy1,1-ethanebisphosphonic acid showing the highest potency with kinetic parameters similar to the reference compound - L-methionine-S-sulfoximine. Moreover, these inhibitors were found to be much more effective against pathogen enzyme than against the human ortholog. Thus, with the bone-targeting properties of the bisphosphonate compounds in mind, this activity/selectivity profile makes these compounds attractive agents for the treatment of bone tuberculosis.
• Pharmaceutically active compounds and methods of use thereof
  申请人：Jiao Jin-An

  公开号：US20070155703A1

  公开（公告）日：2007-07-05

  The invention includes pharmaceutically active compounds and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for treatment or prophylaxis of undesired thrombosis.
• US6828312B2
  申请人：——

  公开号：US6828312B2

  公开（公告）日：2004-12-07
• US7199113B2
  申请人：——

  公开号：US7199113B2

  公开（公告）日：2007-04-03