3-[1-[(2S)-6-amino-1-[4-[4-[4-[2-[4-[3-(diaminomethylideneamino)propyl]triazol-1-yl]acetyl]piperazin-1-yl]-6-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethylamino]-1,3,5-triazin-2-yl]piperazin-1-yl]-1-oxohexan-2-yl]triazol-4-yl]propanoic acid | 1005839-83-7

• 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: 3-[1-[(2S)-6-amino-1-[4-[4-[4-[2-[4-[3-(diaminomethylideneamino)propyl]triazol-1-yl]acetyl]piperazin-1-yl]-6-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethylamino]-1,3,5-triazin-2-yl]piperazin-1-yl]-1-oxohexan-2-yl]triazol-4-yl]propanoic acid
• CAS: 1005839-83-7
• 化学式: C₃₉H₆₂N₁₈O₇
• 分子量: 895.038
• InChiKey: GWMUDXXAENGWRP-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  64
• 可旋转键数：
  28
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  315
• 氢给体数：
  5
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  2-[3-[1-(2-Oxo-2-piperazin-1-ylethyl)triazol-4-yl]propyl]guanidine 、 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 168.0h， 生成 3-[1-[(2S)-6-amino-1-[4-[4-[4-[2-[4-[3-(diaminomethylideneamino)propyl]triazol-1-yl]acetyl]piperazin-1-yl]-6-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethylamino]-1,3,5-triazin-2-yl]piperazin-1-yl]-1-oxohexan-2-yl]triazol-4-yl]propanoic acid
  参考文献：
  名称：

  A Combinatorial Method for Solution-Phase Synthesis of Labeled Bivalent β-Turn Mimics

  摘要：

  Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure 1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key features of these molecules include (i) the possibility of incorporating amino acid side chains corresponding to many of the protein amino acids; (ii) a close correspondence of separations of these side chains to i + 1 to i + 2 residues in turns; (iii) facile adjustment of the side-chain vectors on docking while only influencing two critical degrees of freedom; and (iv) some electrostatic polarity. Fifteen monomers of this type were made via copper-mediated cycloaddition reactions. Solution-phase methodologies were devised to assemble these monomers into bivalent compounds in high purity states (typically >85%) so that they could be used in first-pass biological assays without further purification. The skeleton for forming these bivalent compounds is triazine-based. There is a third site which allowed for introduction of a fluorescent label (library of compounds 2) or an alkyne-functionalized triethylene glycol chain (library of compounds 3) included to promote water-solubility and to allow incorporation of probes via copper-mediated cycloaddition reactions. In the event, two 135-membered libraries were prepared, one consisting of compounds 2 and the other of 3. No protecting groups or coupling agents were required; these attributes of the method were important to allow most of the products to be obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was screened in a fluorescence-activated cell sorting (FACS) assay using cells transfected to overexpress one of the following neurotrophin receptors: TrkA, TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and 2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine turn mimic. Thus, a pharmacological probe for the TrkA receptor has been developed.

  DOI：

  10.1021/ja074717z

文献信息

• A Combinatorial Method for Solution-Phase Synthesis of Labeled Bivalent β-Turn Mimics
  作者：Yu Angell、Dianjun Chen、Fouad Brahimi、H. Uri Saragovi、Kevin Burgess

  DOI：10.1021/ja074717z

  日期：2008.1.1

  Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure 1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key features of these molecules include (i) the possibility of incorporating amino acid side chains corresponding to many of the protein amino acids; (ii) a close correspondence of separations of these side chains to i + 1 to i + 2 residues in turns; (iii) facile adjustment of the side-chain vectors on docking while only influencing two critical degrees of freedom; and (iv) some electrostatic polarity. Fifteen monomers of this type were made via copper-mediated cycloaddition reactions. Solution-phase methodologies were devised to assemble these monomers into bivalent compounds in high purity states (typically >85%) so that they could be used in first-pass biological assays without further purification. The skeleton for forming these bivalent compounds is triazine-based. There is a third site which allowed for introduction of a fluorescent label (library of compounds 2) or an alkyne-functionalized triethylene glycol chain (library of compounds 3) included to promote water-solubility and to allow incorporation of probes via copper-mediated cycloaddition reactions. In the event, two 135-membered libraries were prepared, one consisting of compounds 2 and the other of 3. No protecting groups or coupling agents were required; these attributes of the method were important to allow most of the products to be obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was screened in a fluorescence-activated cell sorting (FACS) assay using cells transfected to overexpress one of the following neurotrophin receptors: TrkA, TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and 2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine turn mimic. Thus, a pharmacological probe for the TrkA receptor has been developed.