tert-butyl (4-((tert-butoxycarbonyl)amino)butyl)(4-(8-hydroxyquinoline-2-carboxamido)butyl)carbamate | 1443681-19-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl (4-((tert-butoxycarbonyl)amino)butyl)(4-(8-hydroxyquinoline-2-carboxamido)butyl)carbamate
• CAS: 1443681-19-3
• 化学式: C₂₈H₄₂N₄O₆
• 分子量: 530.665
• InChiKey: MTXRFQLBBZVLLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.99
• 重原子数：
  38.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  130.09
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-((tert-butoxycarbonyl)amino)butyl)(4-(8-hydroxyquinoline-2-carboxamido)butyl)carbamate 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 以98%的产率得到HQCO-44
  参考文献：
  名称：

  Synthesis and Biological Properties of Quilamines II, New Iron Chelators with Antiproliferative Activities

  摘要：

  To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.

  DOI：

  10.1021/bc4004734
• 作为产物：
  描述：

  [4-(3-cyanopropylamino)butyl]carbamic acid tert-butyl ester 在 ammonium hydroxide 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、2.03 MPa 条件下， 反应 52.0h， 生成 tert-butyl (4-((tert-butoxycarbonyl)amino)butyl)(4-(8-hydroxyquinoline-2-carboxamido)butyl)carbamate
  参考文献：
  名称：

  Synthesis and Biological Properties of Quilamines II, New Iron Chelators with Antiproliferative Activities

  摘要：

  To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.

  DOI：

  10.1021/bc4004734