diethyl (naphthalen-1-ylthio)methylphosphonate | 1451454-50-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: diethyl (naphthalen-1-ylthio)methylphosphonate
• CAS: 1451454-50-4
• 化学式: C₁₅H₁₉O₃PS
• 分子量: 310.354
• InChiKey: GJCNEIWWRLEKEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.16
• 重原子数：
  20.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  diethyl (naphthalen-1-ylthio)methylphosphonate 在 双氧水 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 16.5h， 生成 trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(1"-naphthylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine
  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
• 作为产物：
  描述：

  1-萘磺酰氯 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 乙醚 、 丙酮 为溶剂， 反应 4.5h， 生成 diethyl (naphthalen-1-ylthio)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