diethyl (naphthalen-2-ylsulfonyl)methylphosphonate | 183444-05-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: diethyl (naphthalen-2-ylsulfonyl)methylphosphonate
• 英文别名: diethyl naphthylsulfonyl methylphosphonate；2-(Diethoxyphosphorylmethylsulfonyl)naphthalene
• CAS: 183444-05-5
• 化学式: C₁₅H₁₉O₅PS
• 分子量: 342.353
• InChiKey: BZXSKIOPWCSCHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (naphthalen-2-ylsulfonyl)methylphosphonate 在 sodium hexamethyldisilazane 、 三甲基硅咪唑 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  艾日布林及其中间体的制备方法

  摘要：

  本发明提供了一种艾日布林及其中间的制备方法；特别是采用以萘砜基甲基膦酸二乙酯合成的艾日布林片段A与片段ERB拼接制备化合物P1，收率显著提高，远高于现有技术，并且立体专一性高；此外，本发明在合成中间体化合物P1时，采用了改进的NHK反应，大大降低了铬试剂的用量，不仅降低了成本，而且减少了对环境的污染。

  公开号：

  CN113549101A
• 作为产物：
  描述：

  2-萘硫醇 在 双氧水 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 5.0h， 生成 diethyl (naphthalen-2-ylsulfonyl)methylphosphonate
  参考文献：
  名称：

  Vinyl Sulfone-Based Peptidomimetics as Anti-Trypanosomal Agents: Design, Synthesis, Biological and Computational Evaluation

  摘要：

  A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue Within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the PI, P1', and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times Selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.

  DOI：

  10.1021/jm400294w

文献信息

• REVERSIBLE PROTEASE INHIBITORS
  申请人：ARRIS PHARMACEUTICAL CORPORATION

  公开号：EP0817778A1

  公开（公告）日：1998-01-14
• US5776718A
  申请人：——

  公开号：US5776718A

  公开（公告）日：1998-07-07
• [EN] REVERSIBLE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTEASE REVERSIBLES
  申请人：ARRIS PHARMACEUTICAL CORPORATION

  公开号：WO1996030353A1

  公开（公告）日：1996-10-03

  (EN) The invention relates to novel reversible protease inhibitors. The inhibitors are specific to cysteine proteases. Examples of such inhibitors include compounds with structure (1).(FR) La présente invention décrit de nouveaux inhibiteurs de protéase réversibles. Les inhibiteurs sont spécifiques aux cystéine protéases. De tels inhibiteurs comprennent des composés selon la formule (1).
• Vinyl Sulfone-Based Peptidomimetics as Anti-Trypanosomal Agents: Design, Synthesis, Biological and Computational Evaluation
  作者：Elizabeth Dunny、William Doherty、Paul Evans、J. Paul G. Malthouse、Derek Nolan、Andrew J. S. Knox

  DOI：10.1021/jm400294w

  日期：2013.9.12

  A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue Within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the PI, P1', and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times Selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.
• 艾日布林及其中间体的制备方法
  申请人：博瑞生物医药（苏州）股份有限公司

  公开号：CN113549101A

  公开（公告）日：2021-10-26

  本发明提供了一种艾日布林及其中间的制备方法；特别是采用以萘砜基甲基膦酸二乙酯合成的艾日布林片段A与片段ERB拼接制备化合物P1，收率显著提高，远高于现有技术，并且立体专一性高；此外，本发明在合成中间体化合物P1时，采用了改进的NHK反应，大大降低了铬试剂的用量，不仅降低了成本，而且减少了对环境的污染。