(2S)-3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid | 1101193-38-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 1101193-38-7
• 化学式: C₁₄H₂₆N₄O₇
• 分子量: 362.383
• InChiKey: NYDWDSHNHZCWMW-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  25
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid 在 盐酸 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 methyl 3-[[(2S)-3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-2-[5-[(2-methylpropan-2-yl)oxycarbonyl-pyridin-2-ylamino]pentanoylamino]propanoyl]amino]-3-(4-naphthalen-1-ylphenyl)propanoate
  参考文献：
  名称：

  [EN] LUNG LOCALIZED INHIBITORS OF ALPHA(V)BETA 6
  [FR] INHIBITEURS D'ALPHA (V) BÊTA 6, LOCALISÉS DANS LES POUMONS

  摘要：

  公开号：

  WO2015179823A8
• 作为产物：
  描述：

  BOC-L-丝氨酸 、 叠氮-三聚乙二醇-丙炔基 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 15.0h， 以75%的产率得到(2S)-3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
  参考文献：
  名称：

  Tyrosine-sulfate isosteres of CCR5 N-terminus as tools for studying HIV-1 entry

  摘要：

  The HIV-1 co-receptor CCR5 possesses sulfo-tyrosine (TYS) residues at its N-terminus (Nt) that are required for binding HIV-1 gp120 and mediating viral entry. By using a 14-residue fragment of CCR5 Nt containing two TYS residues, we recently showed that CCR5 Nt binds gp120 through a conserved region specific for TYS moieties and suggested that this site may represent a target for inhibitors and probes of HIV-1 entry. As peptides containing sulfo-tyrosines are difficult to synthesize and handle due to limited stability of the sulfo-ester moiety, we have now incorporated TYS isosteres into CCR5 Nt analogs and assessed their binding to a complex of gp120-CD4 using saturation transfer difference (STD) NMR and surface plasmon resonance (SPR). STD enhancements for CCR5 Nt peptides containing tyrosine sulfonate (TYSN) in complex with gp120-CD4 were very similar to those observed for sulfated CCR5 Nt peptides indicating comparable modes of binding. STD enhancements for phosphotyrosine-containing CCR5 Nt analogs were greatly diminished consistent with earlier findings showing sulfo-tyrosine to be essential for CCR5 Nt binding to gp120. Tyrosine sulfonate-containing CCR5 peptides exhibited reduced water solubility, limiting their use in assay and probe development. To improve solubility, we designed, synthesized, and incorporated in CCR5 Nt peptide analogs an orthogonally functionalized azido tris(ethylenoxy) L-alanine (L-ate-Ala) residue. Through NMR and SPR experiments, we show a 19-residue TYSN-containing peptide to be a functional, hydrolytically stable CCR5 Nt isostere that was in turn used to develop both SPR-based and ELISA assays to screen for inhibitors of CCR5 binding to gp120-CD4. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.10.005