7-benzyl-N-(4-methoxyphenyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine hydrochloride | 1575604-72-6

• 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: 7-benzyl-N-(4-methoxyphenyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine hydrochloride
• 英文别名: 7-benzyl-N-(4-methoxyphenyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine;hydrochloride
• CAS: 1575604-72-6
• 化学式: C₂₁H₂₀N₄O*ClH
• 分子量: 380.877
• InChiKey: CRNLFOMLUQRZMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  62.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 3-amino-4-benzyl-1H-pyrrole-2-carboxylate 在 盐酸 、 三氯氧磷 作用下， 以 乙醚 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 9.25h， 生成 7-benzyl-N-(4-methoxyphenyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine hydrochloride
  参考文献：
  名称：

  Discovery of Antitubulin Agents with Antiangiogenic Activity as Single Entities with Multitarget Chemotherapy Potential

  摘要：

  Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI(50) values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.

  DOI：

  10.1021/ml4004793

文献信息

• Discovery of Antitubulin Agents with Antiangiogenic Activity as Single Entities with Multitarget Chemotherapy Potential
  作者：Aleem Gangjee、Roheeth Kumar Pavana、Michael A. Ihnat、Jessica E. Thorpe、Bryan C. Disch、Anja Bastian、Lora C. Bailey-Downs、Ernest Hamel、Rouli Bai

  DOI：10.1021/ml4004793

  日期：2014.5.8

  Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI(50) values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.