6-[(Di-tert-butoxy-phosphoryl)-difluoro-methyl]-naphthalene-2-carboxylic acid benzyl ester | 219316-46-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-[(Di-tert-butoxy-phosphoryl)-difluoro-methyl]-naphthalene-2-carboxylic acid benzyl ester
• CAS: 219316-46-8
• 化学式: C₂₇H₃₁F₂O₅P
• 分子量: 504.511
• InChiKey: FZAYIOWERSKKHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.07
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6-[(Di-tert-butoxy-phosphoryl)-difluoro-methyl]-naphthalene-2-carboxylic acid benzyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 4-Carbamoyl-4-{[6-(difluoro-phosphono-methyl)-naphthalene-2-carbonyl]-amino}-butyric acid
  参考文献：
  名称：

  Structure-based design and synthesis of small molecule protein–tyrosine phosphatase 1B inhibitors

  摘要：

  Protein-tyrosine phosphatase (PTP) inhibitors are attractive as potential signal transduction-directed therapeutics which may be useful in the treatment of a variety of diseases. We have previously reported the X-ray structure of 1,1-difluoro-1-(2-naphthalenyl)methyl] phosphonic acid (4) complexed with the human the protein-tyrosine phosphatase 1B (PTP1B) and its use in the design of an analogue which binds with higher affinity within the catalytic site (Burke, T. R., Jr. et al. Biochemistry 1996, 35, 15989). In the current study, new naphthyldifluoromethyl phosphonic acids were designed bearing acidic functionality intended to interact with the PTP1B Arg47, which is situated just outside the catalytic pocket. This residue has been shown previously to provide key interactions with acidic residues of phosphotyrosyl-containing peptide substrates. Consistent with trends predicted by molecular dynamics calculations, the new analogues bound with 7- to 14-fold higher affinity than the parent 4, in principal validating the design rationale. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00140-0
• 作为产物：
  描述：

  6-(Di-tert-butoxy-phosphoranecarbonyl)-naphthalene-2-carboxylic acid benzyl ester 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以59%的产率得到6-[(Di-tert-butoxy-phosphoryl)-difluoro-methyl]-naphthalene-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  Structure-based design and synthesis of small molecule protein–tyrosine phosphatase 1B inhibitors

  摘要：

  Protein-tyrosine phosphatase (PTP) inhibitors are attractive as potential signal transduction-directed therapeutics which may be useful in the treatment of a variety of diseases. We have previously reported the X-ray structure of 1,1-difluoro-1-(2-naphthalenyl)methyl] phosphonic acid (4) complexed with the human the protein-tyrosine phosphatase 1B (PTP1B) and its use in the design of an analogue which binds with higher affinity within the catalytic site (Burke, T. R., Jr. et al. Biochemistry 1996, 35, 15989). In the current study, new naphthyldifluoromethyl phosphonic acids were designed bearing acidic functionality intended to interact with the PTP1B Arg47, which is situated just outside the catalytic pocket. This residue has been shown previously to provide key interactions with acidic residues of phosphotyrosyl-containing peptide substrates. Consistent with trends predicted by molecular dynamics calculations, the new analogues bound with 7- to 14-fold higher affinity than the parent 4, in principal validating the design rationale. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00140-0