di-tert-butyl 7-((6-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)pyridin-2-yl)methyl)-1,4,7-triazacyclonane-1,4-dicarboxylate | 1608128-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: di-tert-butyl 7-((6-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)pyridin-2-yl)methyl)-1,4,7-triazacyclonane-1,4-dicarboxylate
• CAS: 1608128-33-1
• 化学式: C₂₆H₄₁N₇O₅
• 分子量: 531.655
• InChiKey: BWBMBSLYJFEAAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  38.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  126.15
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  di-tert-butyl 7-((6-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)pyridin-2-yl)methyl)-1,4,7-triazacyclonane-1,4-dicarboxylate 、 三氟乙酸 以 二氯甲烷 为溶剂， 以100%的产率得到(1-((6-((1,4,7-triazacyclononan-1-yl)methyl)pyridin-2-yl)-methyl)-1H-1,2,3-triazol-4-yl)methanol, TFA Salt
  参考文献：
  名称：

  EGF Receptor-Targeting Peptide Conjugate Incorporating a Near-IR Fluorescent Dye and a Novel 1,4,7-Triazacyclononane-Based ⁶⁴Cu(II) Chelator Assembled via Click Chemistry

  摘要：

  A new Boc-protected 1,4,7-triazacyclononane (TACN)-based pro-chelator compound featuring a "clickable" azidomethylpyridine pendant has been developed as a building block for the construction of multimodal imaging agents. Conjugation to a model alkyne (propargyl alcohol), followed by deprotection, generates a pentadentate ligand, as confirmed by X-ray crystallographic analysis of the corresponding distorted square-pyramidal Cu(II) complex. The ligand exhibits rapid Cu-64(II)-binding kinetics (>95% radiochemical yield in <5 min) and a high resistance to demetalation. It may thus prove suitable for use in Cu-64(II)-based in vivo positron emission tomography (PET). The new chelating building block has been applied to the construction of a bimodal (PET/fluorescence) peptide-based imaging probe targeting the epidermal growth factor (EGF) receptor, which is highly overexpressed on the surface of several types of cancer cells. The probe consists of a hexapeptide sequence, Leu-Ala-Arg-Leu-Leu-Thr (designated "D4"), followed by a Cys-beta-Ala-beta-Ala spacer, then a beta-homopropargylglycine residue with the TACN-based chelator "clicked" to its side chain. A sulfonated near-infrared (NIR) fluorescent cyanine dye (sulfo-Cy5) was introduced at the N-terminus to study the EGF receptor-binding ability of the probe by laser-fluorescence spectroscopy. Binding was also confirmed by coimmunoprecipitation methods, and an apparent dissociation constant (K-d) of ca. 10 nM was determined from radioactivity-based measurements of probe binding to two EGF receptor-expressing cell lines (FaDu and A431). The probe is shown to be a biased or partial allosteric agonist of the EGF receptor, inducing phosphorylation of Thr669 and Tyr992, but not the Tyr845, Tyr998, Tyr1045, Tyr1068, or Tyr1148 residues of the receptor, in the absence of the orthosteric EGF ligand. Additionally, the probe was found to suppress the EGF-stimulated autophosphorylation of these latter residues, indicating that it is also a noncompetitive antagonist.

  DOI：

  10.1021/bc5001388
• 作为产物：
  描述：

  2,6-monobromomethylazidomethylpyridine 在 sodium ascorbate 、 tris(1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl)methylamine 、 potassium carbonate 、 copper(II) sulfate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 1.0h， 生成 di-tert-butyl 7-((6-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)pyridin-2-yl)methyl)-1,4,7-triazacyclonane-1,4-dicarboxylate
  参考文献：
  名称：

  EGF Receptor-Targeting Peptide Conjugate Incorporating a Near-IR Fluorescent Dye and a Novel 1,4,7-Triazacyclononane-Based ⁶⁴Cu(II) Chelator Assembled via Click Chemistry

  摘要：

  A new Boc-protected 1,4,7-triazacyclononane (TACN)-based pro-chelator compound featuring a "clickable" azidomethylpyridine pendant has been developed as a building block for the construction of multimodal imaging agents. Conjugation to a model alkyne (propargyl alcohol), followed by deprotection, generates a pentadentate ligand, as confirmed by X-ray crystallographic analysis of the corresponding distorted square-pyramidal Cu(II) complex. The ligand exhibits rapid Cu-64(II)-binding kinetics (>95% radiochemical yield in <5 min) and a high resistance to demetalation. It may thus prove suitable for use in Cu-64(II)-based in vivo positron emission tomography (PET). The new chelating building block has been applied to the construction of a bimodal (PET/fluorescence) peptide-based imaging probe targeting the epidermal growth factor (EGF) receptor, which is highly overexpressed on the surface of several types of cancer cells. The probe consists of a hexapeptide sequence, Leu-Ala-Arg-Leu-Leu-Thr (designated "D4"), followed by a Cys-beta-Ala-beta-Ala spacer, then a beta-homopropargylglycine residue with the TACN-based chelator "clicked" to its side chain. A sulfonated near-infrared (NIR) fluorescent cyanine dye (sulfo-Cy5) was introduced at the N-terminus to study the EGF receptor-binding ability of the probe by laser-fluorescence spectroscopy. Binding was also confirmed by coimmunoprecipitation methods, and an apparent dissociation constant (K-d) of ca. 10 nM was determined from radioactivity-based measurements of probe binding to two EGF receptor-expressing cell lines (FaDu and A431). The probe is shown to be a biased or partial allosteric agonist of the EGF receptor, inducing phosphorylation of Thr669 and Tyr992, but not the Tyr845, Tyr998, Tyr1045, Tyr1068, or Tyr1148 residues of the receptor, in the absence of the orthosteric EGF ligand. Additionally, the probe was found to suppress the EGF-stimulated autophosphorylation of these latter residues, indicating that it is also a noncompetitive antagonist.

  DOI：

  10.1021/bc5001388