N-(3-aminopropyl)-6-({3,5-bis[(pyridin-2-ylmethyl)amino]cyclohexylamino}methyl)nicotinamide | 780781-66-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(3-aminopropyl)-6-({3,5-bis[(pyridin-2-ylmethyl)amino]cyclohexylamino}methyl)nicotinamide
• CAS: 780781-66-0
• 化学式: C₂₈H₃₈N₈O
• 分子量: 502.663
• InChiKey: DOLHXJCYVVBQHM-LGKQTMLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.91
• 重原子数：
  37.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  129.88
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-马来酰亚胺基丁酸-N-琥珀酰亚胺酯 、 N-(3-aminopropyl)-6-({3,5-bis[(pyridin-2-ylmethyl)amino]cyclohexylamino}methyl)nicotinamide 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以66%的产率得到6-({3,5-bis[(pyridin-2-ylmethyl)amino]cyclohexylamino}methyl)-N-{3-[4-(2,5-dioxo-2,5-dihydropyrrol-1-yl)butyrylamino]propyl}nicotinamide
  参考文献：
  名称：

  Synthesis and Potent Antitumor Activities of Novel 1,3,5-cis,cis-Triaminocyclohexane N-Pyridyl Derivatives

  摘要：

  The iron chelator N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr) was recently reported to display potent antitumor activity. The present study was focused on identifying an adequate bifunctional version of tachpyr as a lead compound for use in antibody-targeted iron depletion tumor therapy. Preparation of tachpyr derivatives having a side chain is reported, and their cytotoxic activity is evaluated in the HeLa cell line. The observed cytotoxity appears dependent on the functionalization site of the tachpyr employed for introducing the protein conjugation. Tachpyr derivatives 14 and 15 having a side chain introduced into the 5-position of the pyridyl ring display more potent cytotoxicity than tachpyr derivatives 7 and 8 having a side chain introduced onto one of the secondary amines. BOC-protected tachpyr derivative 14 exhibited the most potent cytotoxicity against this cancer cell line, which was reasonably comparable to the parent tachpyr. Tachpyr derivative 14 was further converted into bifunctional tachpyr 17 possessing a maleimide linker for conjugation with thiolated monoclonal antibodies (mAbs).

  DOI：

  10.1021/jm040076w
• 作为产物：
  描述：

  {3-[(6-hydroxymethylpyridine-3-carbonyl)amino]propyl}carbamic acid tert-butyl ester 在 盐酸 、 manganese(IV) oxide 、 sodium tetrahydroborate 作用下， 以 1,4-二氧六环 、 乙醇 、 氯仿 、 苯 为溶剂， 反应 65.0h， 生成 N-(3-aminopropyl)-6-({3,5-bis[(pyridin-2-ylmethyl)amino]cyclohexylamino}methyl)nicotinamide
  参考文献：
  名称：

  Synthesis and Potent Antitumor Activities of Novel 1,3,5-cis,cis-Triaminocyclohexane N-Pyridyl Derivatives

  摘要：

  The iron chelator N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr) was recently reported to display potent antitumor activity. The present study was focused on identifying an adequate bifunctional version of tachpyr as a lead compound for use in antibody-targeted iron depletion tumor therapy. Preparation of tachpyr derivatives having a side chain is reported, and their cytotoxic activity is evaluated in the HeLa cell line. The observed cytotoxity appears dependent on the functionalization site of the tachpyr employed for introducing the protein conjugation. Tachpyr derivatives 14 and 15 having a side chain introduced into the 5-position of the pyridyl ring display more potent cytotoxicity than tachpyr derivatives 7 and 8 having a side chain introduced onto one of the secondary amines. BOC-protected tachpyr derivative 14 exhibited the most potent cytotoxicity against this cancer cell line, which was reasonably comparable to the parent tachpyr. Tachpyr derivative 14 was further converted into bifunctional tachpyr 17 possessing a maleimide linker for conjugation with thiolated monoclonal antibodies (mAbs).

  DOI：

  10.1021/jm040076w