4-(2-((2-benzyl-6-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol- 4-yl)amino)ethyl)phenol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-(2-((2-benzyl-6-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol- 4-yl)amino)ethyl)phenol
• 英文别名: 4-[2-[[2-benzyl-6-(2-methyltetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl]amino]ethyl]phenol
• 化学式: C₂₇H₂₄N₈O
• 分子量: 476.541
• InChiKey: FMEBSAZCYJTXQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-甲基-5-(4-硝基苯基)四唑 在 镍 、 potassium carbonate 、 一水合肼 、 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 氯仿 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 13.0h， 生成 4-(2-((2-benzyl-6-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol- 4-yl)amino)ethyl)phenol
  参考文献：
  名称：

  Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion

  摘要：

  The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34(+) cells and CD34(+)CD38(-) cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.04.042

文献信息

• Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion
  作者：Yue Feng、Xiao-Yang Xie、Yi-Qiu Yang、Yu-Tong Sun、Wen-Hui Ma、Peng-Jun Zhou、Zi-Yao Li、Hui-Qiang Liu、Yi-Fei Wang、Yun-Sheng Huang

  DOI：10.1016/j.ejmech.2019.04.042

  日期：2019.7

  The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34(+) cells and CD34(+)CD38(-) cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications. (C) 2019 Elsevier Masson SAS. All rights reserved.