2,3,4,5,6-pentafluorophenyl dichlorophosphate | 17788-07-7

• 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: 2,3,4,5,6-pentafluorophenyl dichlorophosphate
• 英文别名: pentafluorophenyl phosphorodichloridate；Pentafluorophenyl dichlorophosphate；1-dichlorophosphoryloxy-2,3,4,5,6-pentafluorobenzene
• CAS: 17788-07-7
• 化学式: C₆Cl₂F₅O₂P
• 分子量: 300.937
• InChiKey: ZKSOKQHRDFCLSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,3,4,5,6-pentafluorophenyl dichlorophosphate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  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：

  氯化钾 以54%的产率得到
  参考文献：
  名称：

  KABACHNIK M. I.; ZAXAROV L. S.; KUDRYAVTSEV I. YU.; XARCHENKO A. P.; TATA+, IZV. AN CCCP. CEP. XIM., 1979, HO 4, 896-900

  摘要：

  DOI：

文献信息

• [EN] N- [ (2 ' R) -2 ' -DEOXY-2 ' -FLUORO-2 ' -METHYL-P-PHENYL-5 ' -URIDYLYL] -L-ALANINE 1-METHYLETHYL ESTER AND PROCESS FOR ITS PRODUCTION<br/>[FR] ESTER DE N-[(2 ' R) -2' -DÉSOXY-2' -FLUORO-2' -MÉTHYL-P-PHÉNYL-5' -URIDYLYL]-L-ALANINE 1-MÉTHYLÉTHYLE ET SON PROCÉDÉ DE PRODUCTION
  申请人：PHARMASSET INC

  公开号：WO2010135569A1

  公开（公告）日：2010-11-25

  Disclosed herein are nucleoside phosphoramidates of formula 4 and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. Disclosed is also a process for preparing compound represented by formula 4: (Formula 4) wherein P* represents a chiral phosphorus atom, which comprises: a) reacting an isopropyl-alanate, (Formula A), a di-X'-phenylphosphate, (Formula B), 2'-deoxy-2f-fluoro-2'-C-methyluridine, (Formula 3), and a base to obtain a first mixture comprising 4; wherein X is a conjugate base of an acid, n is 0 or 1, and X' is a halogen, b) reacting the first mixture with a protecting compound to obtain a second mixture comprising 4; and c) optionally subjecting the second mixture to crystallization, chromatography or extraction in order to obtain 4.

  本文披露了化学式4的核苷酸磷酰胺及其作为治疗病毒性疾病的药物的用途。这些化合物是RNA依赖性5RNA病毒复制的抑制剂，可作为HCV NS5B聚合酶的抑制剂，HCV复制的抑制剂以及哺乳动物丙型肝炎感染的治疗药物。还披露了一种制备化合物4的方法：（化学式4），其中P*代表手性磷原子，包括：a）反应异丙基-丙氨酸酯（化学式A）、二-X'-苯基磷酸酯（化学式B）、2'-脱氧-2f-氟-2'-C-甲基尿嘧啶（化学式3）和碱以获得含有4的第一混合物；其中X是酸的共轭碱基，n为0或1，X'是卤素；b）将第一混合物与保护化合物反应以获得含有4的第二混合物；c）可选地将第二混合物经结晶、色谱或萃取处理以获得4。
• 一种索非布韦关键中间体的制备方法
  申请人：江苏福瑞生物医药有限公司

  公开号：CN106432327A

  公开（公告）日：2017-02-22

  本发明涉及药物化学技术领域，具体涉及一种索非布韦关键中间体N‑[(S)‑(2,3,4,5,6‑五氟苯氧基)]苯氧基磷酰基‑L‑丙氨酸异丙酯的制备方法。本发明基于反应原理，通过探究L‑丙氨酸异丙酯盐酸盐与苯酚的加料顺序对反应的影响，开发了以二氯磷酸五氟苯酯为起始原料，先与L‑丙氨酸异丙酯盐酸盐反应得到化合物III，再与苯酚拼接，完成化合物I的制备新方法。该方法有效解决了反应条件苛刻，反应设备要求高等问题，反应条件温和，操作简便，产品收率高，纯度好，适用于工业化大规模生产。
• NUCLEOSIDE PHOSPHORAMIDATES
  申请人：Ross Bruce S.

  公开号：US20110251152A1

  公开（公告）日：2011-10-13

  Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

  本文披露了核苷酸磷酰胺及其作为治疗病毒性疾病的药物的用途。这些化合物是RNA依赖性RNA病毒复制的抑制剂，可用作HCV NS5B聚合酶的抑制剂，用于抑制HCV复制并治疗哺乳动物的丙型肝炎感染。
• Nucleoside Phosphoramidates
  申请人：Gilead Pharmasset LLC

  公开号：EP2609923A2

  公开（公告）日：2013-07-03

  Disclosed herein are nucleoside phosphoramidates Sp-4 and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. A process for producing Sp-4 is also disclosed.

  本文公开了核苷磷酸酰胺类化合物Sp-4及其作为治疗病毒性疾病药物的用途。这些化合物是 RNA 依赖性 RNA 病毒复制的抑制剂，可用作 HCV NS5B 聚合酶的抑制剂、HCV 复制的抑制剂和治疗哺乳动物的丙型肝炎感染。 还公开了一种生产 Sp-4 的工艺。
• CRYSTALLINE FORM OF SOFOSBUVIR
  申请人：Gilead Pharmasset LLC

  公开号：EP3321275A1

  公开（公告）日：2018-05-16

  Disclosed herein is crystalline phosphoramidate Sp-4 (Sofosbuvir) of the formula below. This compound is an inhibitor of RNA-dependent 5 RNA viral replication and is useful as inhibitor of HCV NS5B polymerase, as inhibitor of HCV replication and for treatment of hepatitis C infection in mammals. This compound can be used in combination with another antiviral agent, such as an HCV NS3 protease inhibitor or an HCV NS5A inhibitor.

  本文公开的是下式的结晶磷酰胺 Sp-4（索非布韦）。 该化合物是一种 RNA 依赖性 5 RNA 病毒复制抑制剂，可用作 HCV NS5B 聚合酶抑制剂、HCV 复制抑制剂和哺乳动物丙型肝炎感染的治疗药物。该化合物可与另一种抗病毒药物（如 HCV NS3 蛋白酶抑制剂或 HCV NS5A 抑制剂）联合使用。