5-nitro-m-xylylene bisphosphonic acid tetramethyl ester | 262863-44-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-nitro-m-xylylene bisphosphonic acid tetramethyl ester
• 英文别名: tetramethyl 1-nitro-benzene-3,5-bis(methylphosphonate)；1,3-Bis(dimethoxyphosphorylmethyl)-5-nitrobenzene
• CAS: 262863-44-5
• 化学式: C₁₂H₁₉NO₈P₂
• 分子量: 367.232
• InChiKey: QNNXXEYZIDKPJD-UHFFFAOYSA-N

物化性质

• 熔点：
  103-104 °C
• 沸点：
  521.6±50.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-nitro-m-xylylene bisphosphonic acid tetramethyl ester 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以97%的产率得到5-amino-m-xylylenebis(phosphonic acid) tetramethyl ester
  参考文献：
  名称：

  高亲和力共聚物通过表面识别抑制消化酶

  摘要：

  该文献提供了构建用于消化酶的聚合物表面粘合剂的一般方法。两个突出的部分，即共聚物组成的改性和最有效的抑制剂的筛选试验，都适合于平行化。上氨基酸的选择性共聚单体的适当的选择，它们的自由基共聚，和所得到的共聚物库用于高效酶抑制随后的筛选概念铰链。开发了一种用于共聚过程的微型合成程序，该程序可生产水溶性亲和聚合物，该聚合物可在室温下保存多年。最初的平行筛选是在标准酶分析中进行的，以鉴定多聚体抑制剂，然后对其进行IC 50的测定。目标酶的值。对于除弹性蛋白酶以外的所有消化酶，都发现了许多聚合物抑制剂，其中一些对一种或两种蛋白质靶具有选择性。由于最好的抑制剂的关键单体与活性位点直接附近的氨基酸残基结合，因此我们得出结论，共聚物对周围环境的有效覆盖至关重要。对酶活性的强烈干扰是通过阻止底物进入和产物进入和离开活性位点而引起的。

  DOI：

  10.1021/acs.biomac.7b00162
• 作为产物：
  描述：

  5-硝基间二甲苯 在 偶氮二异丁腈 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 为溶剂， 反应 3.0h， 生成 5-nitro-m-xylylene bisphosphonic acid tetramethyl ester
  参考文献：
  名称：

  Optimization of a Synthetic Arginine Receptor. Systematic Tuning of Noncovalent Interactions

  摘要：

  The simple arginine binder I could be optimized by strengthening pi -cation as well as electrostatic interactions. Electron-donating or -withdrawing substituents in the 5-position provide experimental evidence for T-cation interactions, because binding energies increase by up to 0.6 kcal/mol due to a single benzene - guanidinium interaction. Even more effective is the introduction of a third phosphonate functionality at the correct distance, so that the guanidinium cation is recognized by optimal electrostatic and hydrogen bond interactions. Monte Carlo simulations and NOESY experiments confirm the expected complex geometries. The optimized host molecule 8 binds arginine half an order of magnitude more efficiently than the parent molecule.

  DOI：

  10.1021/jo0156161

文献信息

• Acyclic Analogues of Deoxyadenosine 3‘,5‘-Bisphosphates as P2Y₁ Receptor Antagonists
  作者：Yong-Chul Kim、Carola Gallo-Rodriguez、Soo-Yeon Jang、Erathodiyil Nandanan、Mary Adams、T. Kendall Harden、José L. Boyer、Kenneth A. Jacobson

  DOI：10.1021/jm9905211

  日期：2000.2.1

  trans-olefinic groups greatly reduced antagonist potency at the P2Y(1) receptor. Analogues containing a diethanolamine amide group and an aryl di(methylphosphonate) were both less potent than 10 as antagonists, with IC(50) values of 14 and 16 microM, respectively, and no agonist activity was observed for these analogues. Thus, the ribose moiety is clearly not essential for recognition by the turkey P2Y(1) receptor

  P2Y(1) 受体由 ADP 激活，存在于内皮细胞、平滑肌、上皮细胞、肺、胰腺、血小板和中枢神经系统中。借助分子建模，我们设计了核苷酸类似物，可作为该亚型的选择性拮抗剂。本研究检验了以下假设：核糖环的无环修饰已被证明对于核苷抗病毒药物（如更昔洛韦）非常成功，可推广到 P2Y 受体配体。具体而言，发现 P2Y(1) 受体的结合位点具有足够的适应性，允许用连接到腺嘌呤 9 位的无环脂肪族和芳香族链取代核糖基团。制备了三组具有不同侧链结构的腺嘌呤衍生物，每组含有两个对称的磷酸酯或膦酸酯基团。通过无环衍生物在刺激火鸡红细胞膜中磷脂酶C时充当激动剂或拮抗剂的能力证明了生物活性。 [0073] 一种无环N(6)-甲基腺嘌呤衍生物，2-[2-(6-甲基氨基-嘌呤-9-基)-乙基]-丙烷-1, 3-二氧基(磷酸二铵)(10)，含有异戊基二磷酸部分，是 P2Y(1) 受体的完全拮抗剂，IC(50) 值为 1
• Arginine- and Lysine-Specific Polymers for Protein Recognition and Immobilization
  作者：Christian Renner、Jacob Piehler、Thomas Schrader

  DOI：10.1021/ja0560229

  日期：2006.1.1

  Free radical polymerization of methacrylamide-based bisphosphonates turns weak arginine binders into powerful polymeric protein receptors. Dansyl-labeled homo- and copolymers with excellent water solubility are accessible through a simple copolymerization protocol. Modeling studies point to a striking structural difference between the stiff rodlike densely packed homopolymer 1 and the flexible copolymer 2 with spatially separated bisphosphonate units. Fluorescence titrations in buffered aqueous solution (pH = 7.0) confirm the superior affinity of the homopolymer toward oligoarginine peptides reaching nanomolar K-D values for the Tat peptide. Basic proteins are bound almost equally well by 1 and 2 with micromolar affinities, with the latter producing much more soluble complexes. The Arg selectivity of the monomer is transferred to the polymer, which binds Arg-rich proteins 1 order of magnitude tighter than lysine-rich pendants of comparable pl, size, and (Arg/Lys vs Glu/Asp) ratio. Noncovalent deposition of both polymers on glass substrates via polyethyleneimine layers results in new materials suitable for peptide and protein immobilization. RlfS measurements allow calculation of association constants K-a as well as dissociation kinetics k(D). They generally confirm the trends already found in free solution. Close inspection of electrostatic potential surfaces suggest that basic domains favor protein binding on the flat surface. The high specificity of the bisphosphonate polymers toward basic proteins is demonstrated by comparison with polyvinyl sulfate, which has almost no effect in RlfS experiments. Thus, copolymerization of few different comonomer units without cross-linking enables surface recognition of basic proteins in free solution as well as their effective immobilization on surfaces.
• Structure−Activity Relationships of Pyridoxal Phosphate Derivatives as Potent and Selective Antagonists of P2X₁ Receptors
  作者：Yong-Chul Kim、Sean G. Brown、T. Kendall Harden、José L. Boyer、George Dubyak、Brian F. King、Geoffrey Burnstock、Kenneth A. Jacobson

  DOI：10.1021/jm9904203

  日期：2001.2.1

  Novel analogues of the P2 receptor antagonist pyridoxal-5'-phosphate 6-azophcnyl-2',5'-disulfonate (2) were synthesized and studied as antagonists in functional assays at recombinant rat P2X(1), P2X(2), and P2X(3) receptors expressed in Xenopus oocytes lion flux stimulation) and at turkey erythrocyte P2Y(1) receptors (phospholipase C activation). Selected compounds were also evaluated as antagonists of ion flux and the opening of a large pore at the recombinant human P2X(7) receptor. Modifications were made in the 4-aldehyde and 5'-phosphate groups of the pyridoxal moiety: i.e. a CH2OH group at the 4-position in pyridoxine was either condensed as a cyclic phosphate or phosphorylated separately to form a bisphosphate, which reduced potency at P2 receptors. 5-Methylphosphonate substitution, anticipated to increase stability to hydrolysis, preserved P2 receptor potency. At the g-position, halo, carboxylate, sulfonate, and phosphonate variations made on the phenylazo ring modulated potency at P2 receptors. The p-carboxyphenylazo analogue, 4, of phosphate 2 displayed an IC50 value of 9 nM at recombinant P2X(1) receptors and was 1300-, 16-, and >10000-fold selective for P2X(1) versus P2X(2), P2X(3), and P2Y(1) subtypes, respectively. The corresponding Ei-methylphosphonate was equipotent at P2X(1) receptors. The 5-methylphosphonate analogue containing a 6-[3,5-bis(methylphosphonate)]phenylazo moiety, 9, had IC50 values of 11 and 25 nM at recombinant P2X(1) and P2X(3) receptors, respectively. The analogue containing a phenylazo 4-phosphonate group, 11, was also very potent at both P2X(1) and P2X(3) receptors. However, the corresponding 2,5-disulfonate analogue, 10, was 28-fold selective for P2X(1) versus P2X(3) receptors. None of the analogues were more potent at P2X(7) and P2Y(1) receptors than 2, which acted in the micromolar range at these two subtypes.
• High-Affinity Copolymers Inhibit Digestive Enzymes by Surface Recognition
  作者：Patrick Gilles、Kirstin Wenck、Inga Stratmann、Michael Kirsch、Daniel A. Smolin、Torsten Schaller、Herbert de Groot、Arno Kraft、Thomas Schrader

  DOI：10.1021/acs.biomac.7b00162

  日期：2017.6.12

  except elastase, a number of polymer inhibitors were found, some of which were selective toward one or two protein targets. Since the key monomers of the best inhibitors bind to amino acid residues in the direct vicinity of the active site, we conclude that efficient coverage of the immediate environment by the copolymers is critical. Strong interference with enzymatic activity is brought about by blocking

  该文献提供了构建用于消化酶的聚合物表面粘合剂的一般方法。两个突出的部分，即共聚物组成的改性和最有效的抑制剂的筛选试验，都适合于平行化。上氨基酸的选择性共聚单体的适当的选择，它们的自由基共聚，和所得到的共聚物库用于高效酶抑制随后的筛选概念铰链。开发了一种用于共聚过程的微型合成程序，该程序可生产水溶性亲和聚合物，该聚合物可在室温下保存多年。最初的平行筛选是在标准酶分析中进行的，以鉴定多聚体抑制剂，然后对其进行IC 50的测定。目标酶的值。对于除弹性蛋白酶以外的所有消化酶，都发现了许多聚合物抑制剂，其中一些对一种或两种蛋白质靶具有选择性。由于最好的抑制剂的关键单体与活性位点直接附近的氨基酸残基结合，因此我们得出结论，共聚物对周围环境的有效覆盖至关重要。对酶活性的强烈干扰是通过阻止底物进入和产物进入和离开活性位点而引起的。
• Optimization of a Synthetic Arginine Receptor. Systematic Tuning of Noncovalent Interactions
  作者：Stephan Rensing、Markus Arendt、Andreas Springer、Thomas Grawe、Thomas Schrader

  DOI：10.1021/jo0156161

  日期：2001.8.1

  The simple arginine binder I could be optimized by strengthening pi -cation as well as electrostatic interactions. Electron-donating or -withdrawing substituents in the 5-position provide experimental evidence for T-cation interactions, because binding energies increase by up to 0.6 kcal/mol due to a single benzene - guanidinium interaction. Even more effective is the introduction of a third phosphonate functionality at the correct distance, so that the guanidinium cation is recognized by optimal electrostatic and hydrogen bond interactions. Monte Carlo simulations and NOESY experiments confirm the expected complex geometries. The optimized host molecule 8 binds arginine half an order of magnitude more efficiently than the parent molecule.