N-(3-fluorophenyl)-2-{4-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(3-fluorophenyl)-2-{4-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide
• 英文别名: 4-Aminopyrazole quinazoline, 5；N-(3-fluorophenyl)-2-[4-[[7-[3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy]-6-methoxyquinazolin-4-yl]amino]pyrazol-1-yl]acetamide
• 化学式: C₂₈H₃₂FN₇O₄
• 分子量: 549.605
• InChiKey: ACDXDLIQFJBPHN-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(4-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-1-yl)-N-(3-fluorophenyl)acetamide 、 D-脯氨醇 在 potassium iodide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 N-(3-fluorophenyl)-2-{4-[(7-{3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide
  参考文献：
  名称：

  Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: Selective inhibitors of Aurora B kinase with potent anti-tumor activity

  摘要：

  A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.002

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] DERIVES DE QUINAZOLINE POUR LE TRAITEMENT DU CANCER
  申请人：ASTRAZENECA AB

  公开号：WO2004094410A1

  公开（公告）日：2004-11-04

  Quinazoline derivatives of formula (I); for use in the treatment of proliferative diseases such as cancer and in the preparation of medicaments for use in the treatment of proliferative diseases, and to processes for their preparation, as well as pharmaceutical compositions containing them as active ingredient.

  公式（I）的喹唑啉衍生物；用于治疗癌症等增殖性疾病，并用于制备用于治疗增殖性疾病的药物，以及它们的制备方法，以及含有它们作为活性成分的药物组合物。
• Chemical compounds
  申请人：Heron Murdoch Nicola

  公开号：US20060270692A1

  公开（公告）日：2006-11-30

  Quinazoline derivatives of formula (I); for use in the treatment of proliferative diseases such as cancer and in the preparation of medicaments for use in the treatment of proliferative diseases, and to process for their preparation, as well as pharmaceutical compositions containing them as active ingredient.

  公式(I)的喹唑啉衍生物；用于治疗增殖性疾病，例如癌症，并用于制备用于治疗增殖性疾病的药物，以及其制备过程，以及包含它们作为活性成分的制药组合物。
• QUINAZOLINE DERIVATIVES FOR TREATMENT OF CANCER
  申请人：AstraZeneca AB

  公开号：EP1613619B1

  公开（公告）日：2008-03-26
• EP1613619A1
  申请人：——

  公开号：EP1613619A1

  公开（公告）日：2006-01-11
• US7691867B2
  申请人：——

  公开号：US7691867B2

  公开（公告）日：2010-04-06