[(4-chlorophenylamino)methyl]-1,1-bisphosphonic acid | 59611-67-5

• 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: [(4-chlorophenylamino)methyl]-1,1-bisphosphonic acid
• 英文别名: (4-Chlorophenylamino)methylenediphosphonic acid；[(4-chloroanilino)-phosphonomethyl]phosphonic acid
• CAS: 59611-67-5
• 化学式: C₇H₁₀ClNO₆P₂
• 分子量: 301.56
• InChiKey: PPOZCMYPJMEBPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1,1-二氯-N-(4-氯苯基)甲亚胺 在 盐酸 作用下， 生成 [(4-chlorophenylamino)methyl]-1,1-bisphosphonic acid
  参考文献：
  名称：

  Gross,H. et al., Journal fur praktische Chemie (Leipzig 1954), 1976, vol. 318, p. 116 - 126

  摘要：

  DOI：

文献信息

• Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors
  作者：Marilena Tauro、Antonio Laghezza、Fulvio Loiodice、Mariangela Agamennone、Cristina Campestre、Paolo Tortorella

  DOI：10.1016/j.bmc.2013.08.054

  日期：2013.11

  The complexity of matrix metalloproteinase inhibitors (MMPIs) design derives from the difficulty in carefully addressing their inhibitory activity towards the MMP isoforms involved in many pathological conditions. In particular, specific metalloproteinases, such as MMP-2 and MMP-9, are key regulators of the 'vicious cycle' occurring between tumor metastases growth and bone remodeling. In an attempt to devise new approaches to selective inhibitor derivatives, we describe novel bisphosphonate bone seeking MMP inhibitors (BP-MMPIs), capable to be selectively targeted and to overcome undesired side effects of broad spectrum MMPIs.In vitro activity (IC50 values) for each inhibitor was determined against MMP-2, -8, -9 and -14, because of their relevant role in skeletal development and renewal. The results show that BP-MMPIs reached IC50 values of enzymatic inhibition in the low micromolar range. Computational studies, used to rationalize some trends in the observed inhibitory profiles, suggest a possible differential binding mode in MMP-2 that explains the selective inhibition of this isoform.In addition, survival assay was conducted on J774 cell line, a well known model system used to evaluate the structure-activity relationship of BPs for inhibiting bone resorption. The resulting data, confirming the specific activity of BP-MMPIs, and their additional proved propensity to bind hydroxyapatite powder in vitro, suggest a potential use of BP-MMPIs in skeletal malignancies. (C) 2013 Elsevier Ltd. All rights reserved.
• Tailoring the Structure of Aminobisphosphonates To Target Plant P5C Reductase
  作者：Giuseppe Forlani、Andrea Occhipinti、Łukasz Berlicki、Gabriela Dziedzioła、Anna Wieczorek、Paweł Kafarski

  DOI：10.1021/jf800029t

  日期：2008.5.1

  Using the structure of (3,5-dichlorophenyl)aminomethylenebisphosphonic acid as a lead compound, 25 new phosphonates were synthesized and evaluated as possible inhibitors of Arabidopsis thaliana delta(1)-pyrroline-5-carboxylate (P5C) reductase. Derivatives substituted in the phenyl ring retained the inhibitory potential, though to a different extent. On the contrary any variation in the scaffold, i.e., the replacement of the second phosphonate moiety with a hydroxyl or an amino residue, resulted in a significant loss of biological activity. The availability of several structures capable of interfering with the catalytic mechanism in the micromolar to millimolar range allowed a proper structure-activity relationship analysis, leading us to hypothesize about the steric and electronic requirements for maintenance or enhancement of the inhibitory properties. Reversal experiments with suspension cultured cells provided evidence for the occurrence of enzyme inhibition in vivo. Because in higher plants the step catalyzed by P5C reductase is shared by all pathways leading to proline synthesis, these compounds may be exploited for the design of new substances endowed with herbicidal activity.
• 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.
• Gross,H. et al., Journal fur praktische Chemie (Leipzig 1954), 1976, vol. 318, p. 116 - 126
  作者：Gross,H. et al.

  DOI：——

  日期：——