triethyl methylphosphinomethylenephosphonate | 155051-26-6

• 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: triethyl methylphosphinomethylenephosphonate
• 英文别名: 1-Diethoxyphosphoryl-1-[ethoxy(methyl)phosphoryl]ethene
• CAS: 155051-26-6
• 化学式: C₉H₂₀O₅P₂
• 分子量: 270.202
• InChiKey: JGOLIHDBVPPLEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  triethyl methylphosphinomethylenephosphonate 、 3,4-二氯苄溴 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Bisphosphonate inhibitors of ATP-mediated HIV-1 reverse transcriptase catalyzed excision of chain-terminating 3′-azido, 3′-deoxythymidine: A QSAR investigation

  摘要：

  We report the results of an investigation of the inhibition of the ATP-mediated HIV-1 reverse transcriptase catalyzed phosphorolysis in vitro of AZT from AZT-terminated DNA primers by a series of 42 bisphosphonates. The four most active compounds possess neutral, halogen-substituted phenyl or biphenyl sidechains and have IC50 values < 1 mu M in excision inhibition assays. Use of two comparative molecular similarity analysis methods to analyze these inhibition results yielded a classification model with an overall accuracy of 94%, and a regression model having good accord with experiment (q(2) = 0.63, r(2) = 0.91), with the experimental activities being predicted within, on average, a factor of 2. The most active species had little or no toxicity against three human cell lines (IC50avg > 200 mu M). These results are of general interest since they suggest that it may be possible to develop potent bisphosphonate-based AZT-excision inhibitors with little cellular toxicity, opening up a new route to restoring AZT sensitivity in otherwise resistant HIV-1 strains. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.047

文献信息

• US5635495A
  申请人：——

  公开号：US5635495A

  公开（公告）日：1997-06-03
• Bisphosphonate inhibitors of ATP-mediated HIV-1 reverse transcriptase catalyzed excision of chain-terminating 3′-azido, 3′-deoxythymidine: A QSAR investigation
  作者：Yongcheng Song、Julian M.W. Chan、Zev Tovian、Aaron Secrest、Eva Nagy、Kilannin Krysiak、Kyle Bergan、Michael A. Parniak、Eric Oldfield

  DOI：10.1016/j.bmc.2008.08.047

  日期：2008.10

  We report the results of an investigation of the inhibition of the ATP-mediated HIV-1 reverse transcriptase catalyzed phosphorolysis in vitro of AZT from AZT-terminated DNA primers by a series of 42 bisphosphonates. The four most active compounds possess neutral, halogen-substituted phenyl or biphenyl sidechains and have IC50 values < 1 mu M in excision inhibition assays. Use of two comparative molecular similarity analysis methods to analyze these inhibition results yielded a classification model with an overall accuracy of 94%, and a regression model having good accord with experiment (q(2) = 0.63, r(2) = 0.91), with the experimental activities being predicted within, on average, a factor of 2. The most active species had little or no toxicity against three human cell lines (IC50avg > 200 mu M). These results are of general interest since they suggest that it may be possible to develop potent bisphosphonate-based AZT-excision inhibitors with little cellular toxicity, opening up a new route to restoring AZT sensitivity in otherwise resistant HIV-1 strains. (C) 2008 Elsevier Ltd. All rights reserved.