hydroxy(naphthalen-1-yl)methylphosphonic acid | 115308-68-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: hydroxy(naphthalen-1-yl)methylphosphonic acid
• 英文别名: (hydroxy-[1]naphthyl-methyl)-phosphonic acid；(Hydroxy-[1]naphthyl-methyl)-phosphonsaeure；[hydroxy(naphthalen-1-yl)methyl]phosphonic acid
• CAS: 115308-68-4
• 化学式: C₁₁H₁₁O₄P
• mdl: MFCD27941793
• 分子量: 238.18
• InChiKey: AXIBZLYWMBUYRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  diethyl hydroxy(naphthalen-1-yl)methylphosphonate 在 三甲基氯硅烷 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 84.0h， 以52%的产率得到hydroxy(naphthalen-1-yl)methylphosphonic acid
  参考文献：
  名称：

  Inhibition of purple acid phosphatase with α-alkoxynaphthylmethylphosphonic acids

  摘要：

  Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyse the hydrolysis of a range of phosphorylated substrates. Human PAP is a major histochemical marker for the diagnosis of osteoporosis. In patients suffering from this disorder, PAP activity contributes to increased bone resorption and, therefore, human PAP is a key target for the development of anti-osteoporotic drugs. This manuscript describes the design and synthesis of derivatives of 1-naphthylmethylphosphonic acids as inhibitors of PAP. The K(i) values of these compounds are as low as 4 mu M, the lowest reported to date for a PAP inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.125

文献信息

• Phosphonate-containing inhibitors of tyrosine-specific protein kinases
  作者：Terrence R. Burke、Zhen Hong Li、Joseph B. Bolen、Victor E. Marquez

  DOI：10.1021/jm00109a008

  日期：1991.5

  Tyrosine-specific protein kinases (TPK) are important signal transducing enzymes involved in normal cellular growth and differentiation and have been implicated in the etiology of a number of human neoplastic processes. Efforts to develop agents which inhibit the function of these enzymes by interfering with the binding of substrate have been limited by the lack of detailed three-dimensional structural

  酪氨酸特异性蛋白激酶（TPK）是参与正常细胞生长和分化的重要信号转导酶，已与许多人类肿瘤过程的病因有关。由于缺乏详细的三维结构数据，限制了通过干扰底物的结合来抑制这些酶功能的试剂的开发工作受到了限制。许多底物结合的抑制剂共享一个共同的苯乙烯核1，该苯乙烯核被假定为酪氨酸的构象约束类似物。为了根据该假设开发高亲和力的化合物，合成了许多衍生物，其中将甲基膦酸酯（4a-c）或（羟甲基）膦酸酯（3a-c）附加到苯乙烯-芳族化合物的4位上包含部分。该方法的目的是制备水解稳定的类似物，该类似物表达在酪氨酸本身的磷酸化过程中存在的其他酶识别特征。当针对A-431衍生的表皮生长因子受体（EGFR）或p56lck的自磷酸化（兔肌肉烯醇化酶的自磷酸化和转磷酸化）进行测定时，没有类似物显示出抑制活性直至最大测试浓度（1000 microM）。此外，还在类似条件下测试了一系列基于萘的抑制剂，包括（1-萘基羟甲基）
• Small ligands interacting with the phosphotyrosine binding pocket of the Src SH2 protein
  作者：Pierre Deprez、Eliane Mandine、Dominique Gofflo、Stéphane Meunier、Dominique Lesuisse

  DOI：10.1016/s0960-894x(02)00140-3

  日期：2002.5

  Various small fragments bearing phosphate, phosphonate or phosphonic acid moieties have been prepared through parallel synthesis and their binding potencies evaluated on the Sre SH2 protein using a BIAcore assay. This provided us insight into the requirement of the Src SH2 pTyr binding pocket and some promising small ligands have been characterised. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Novel hydroxyphosphonate inhibitors of CD-45 tyrosine phosphatase
  作者：Roger F. Frechette、Caridad Ackerman、Scott Beers、Rich Look、John Moore

  DOI：10.1016/s0960-894x(97)00390-9

  日期：1997.9

  CD-45 tyrosine phosphatase [E.C. 3.1.3.48] is an important player in the regulation of cell activation and proliferation in hematopoetic cells. As part of a program in immune response modulation, we prepared the first series of small organic molecule inhibitors of CD-45. The preparation and in vitro screening of these hydroxyphosphonates is described herein. (C) 1997 Elsevier Science Ltd.
• BURKE, TERRENCE R. (JR);LI, ZHEN-HONG;BOLEN, JOSEPH B.;MARGUEZ, VICTOR E., J. MED. CHEM., 34,(1991) N, C. 1577-1581
  作者：BURKE, TERRENCE R. (JR)、LI, ZHEN-HONG、BOLEN, JOSEPH B.、MARGUEZ, VICTOR E.

  DOI：——

  日期：——
• Craniades; Rumpf, Bulletin de la Societe Chimique de France, 1952, p. 1063
  作者：Craniades、Rumpf

  DOI：——

  日期：——