1-[Chloro(phenylmethoxy)phosphoryl]oxy-4-nitrobenzene | 133878-46-3

• 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: 1-[Chloro(phenylmethoxy)phosphoryl]oxy-4-nitrobenzene
• CAS: 133878-46-3
• 化学式: C₁₃H₁₁ClNO₅P
• 分子量: 327.661
• InChiKey: NVMFTLJYNTZTPN-UHFFFAOYSA-N

物化性质

• 沸点：
  454.1±55.0 °C(Predicted)
• 密度：
  1.437±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[Chloro(phenylmethoxy)phosphoryl]oxy-4-nitrobenzene 在 三乙烯二胺 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.0h， 生成 benzyl N-[hydroxy-(4-nitrophenoxy)phosphoryl]oxycarbamate
  参考文献：
  名称：

  Covalent Inhibition of Serine β-Lactamases by Novel Hydroxamic Acid Derivatives

  摘要：

  The effectiveness of beta-lactam antibiotics is greatly limited by the ability of bacteria to produce beta-lactamases. These enzymes catalyze the hydrolysis of beta-lactams and thus loss of their antibiotic activity. The search for inhibitors of beta-lactamases began soon after beta-lactams were introduced into medical practice and continues today. Some time ago, we introduced a new class of covalent serine beta-lactamase inhibitors, the O-aryloxycarbonyl hydroxamates, that inactivated these enzymes by a unique mechanism in which the active site became cross-linked. We describe in this paper some new variants of this class of inhibitor. First, we investigated compounds in which more polar hydroxamates were incorporated. These were generally not more active than the original compounds against representative class A and class C beta-lactamases, but one of them, 1-(benzoyl)-O-(phenoxycarbonyl)-3-hydroxyurea, was significantly more stable in solution, thus revealing a useful platform for further design. Second, we describe a series of O-(arylphosphoryl) hydroxamates that are also irreversible inactivators of class A and class C beta-lactamases, by phosphorylation of the enzyme, as revealed by mass spectra. These compounds did not, however, cross-link the enzyme active site A striking feature of their structure-activity profile was that hydroxamate remained the leaving group on enzyme phosphorylation rather than aryloxide, even though the aryloxide was intrinsically the better leaving group, as indicated by pK(a) values and demonstrated by the products of hydrolysis in free solution. Model building suggested that this phenomenon arises from the relative affinity of the enzyme active site components for the two leaving groups. The results obtained for both groups of inhibitors are important for further optimization of these inhibitors.

  DOI：

  10.1021/bi4003887
• 作为产物：
  描述：

  4-硝基苯二氯化磷 、 苯甲醇 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-[Chloro(phenylmethoxy)phosphoryl]oxy-4-nitrobenzene
  参考文献：
  名称：

  Covalent Inhibition of Serine β-Lactamases by Novel Hydroxamic Acid Derivatives

  摘要：

  The effectiveness of beta-lactam antibiotics is greatly limited by the ability of bacteria to produce beta-lactamases. These enzymes catalyze the hydrolysis of beta-lactams and thus loss of their antibiotic activity. The search for inhibitors of beta-lactamases began soon after beta-lactams were introduced into medical practice and continues today. Some time ago, we introduced a new class of covalent serine beta-lactamase inhibitors, the O-aryloxycarbonyl hydroxamates, that inactivated these enzymes by a unique mechanism in which the active site became cross-linked. We describe in this paper some new variants of this class of inhibitor. First, we investigated compounds in which more polar hydroxamates were incorporated. These were generally not more active than the original compounds against representative class A and class C beta-lactamases, but one of them, 1-(benzoyl)-O-(phenoxycarbonyl)-3-hydroxyurea, was significantly more stable in solution, thus revealing a useful platform for further design. Second, we describe a series of O-(arylphosphoryl) hydroxamates that are also irreversible inactivators of class A and class C beta-lactamases, by phosphorylation of the enzyme, as revealed by mass spectra. These compounds did not, however, cross-link the enzyme active site A striking feature of their structure-activity profile was that hydroxamate remained the leaving group on enzyme phosphorylation rather than aryloxide, even though the aryloxide was intrinsically the better leaving group, as indicated by pK(a) values and demonstrated by the products of hydrolysis in free solution. Model building suggested that this phenomenon arises from the relative affinity of the enzyme active site components for the two leaving groups. The results obtained for both groups of inhibitors are important for further optimization of these inhibitors.

  DOI：

  10.1021/bi4003887

文献信息

• HCV POLYMERASE INHIBITORS
  申请人：MEDIVIR AB

  公开号：US20160271160A1

  公开（公告）日：2016-09-22

  The invention provides compounds of the formula: wherein B is a nucleobase selected from the groups (a) to (d): and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

  本发明提供了以下式子的化合物：其中B是从组（a）到（d）中选择的核碱基：其他变量如权利要求中所定义，该化合物可用于治疗或预防丙型肝炎病毒感染及相关方面。
• Krishnan, B. Radha; Winwood, D.; Bodor, N., Synthetic Communications, 1990, vol. 20, # 17, p. 2653 - 2658
  作者：Krishnan, B. Radha、Winwood, D.、Bodor, N.

  DOI：——

  日期：——
• KRISHNAN, B. RADHA;WINWOOD, D.;BODOR, N., SYNTH. COMMUN., 20,(1990) N7, C. 2653-2658
  作者：KRISHNAN, B. RADHA、WINWOOD, D.、BODOR, N.

  DOI：——

  日期：——
• US9828408B2
  申请人：——

  公开号：US9828408B2

  公开（公告）日：2017-11-28