amino-(2-chloropyridin-3-yl)methylcyanamide | 333736-94-0

• 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: amino-(2-chloropyridin-3-yl)methylcyanamide
• 英文别名: amino-(2-chloro-pyridin-3-yl)-methylcyanamide；2-chloro-N-cyanonicotinamidine；2-chloro-N'-cyanopyridine-3-carboximidamide
• CAS: 333736-94-0
• 化学式: C₇H₅ClN₄
• 分子量: 180.596
• InChiKey: BMALJVWMQMRIAI-UHFFFAOYSA-N

物化性质

• 沸点：
  292.5±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  amino-(2-chloropyridin-3-yl)methylcyanamide 在 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 40.5h， 生成 N-(5-cyclohexyl-2-methoxyphenyl)-4-methyl-3-(3-(4-(methylamino)-1,3,5-triazin-2-yl)pyridin-2-yloxy)benzamide
  参考文献：
  名称：

  Evolution of a Highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor

  摘要：

  Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well understood. In order to evaluate the therapeutic utility of inhibiting Tie-2 signaling, we developed a series of potent and orally bioavailable small molecule Tie-2 kinase inhibitors with selectivity over other kinases, especially those that are believed to be important for tumor angiogenesis. Our earlier work provided pyridinyl pyrimidine 6 as a potent, nonselective Tie-2 inhibitor that was designed on the basis of X-ray cocrystal structures of KDR inhibitors 34 (triazine) and 35 (nicotinamide). Lead optimization resulted in pyridinyl triazine 63, which exhibited > 30-fold selectivity over a panel of kinases, good oral exposure, and in vivo inhibition of Tie-2 phosphorylation.

  DOI：

  10.1021/jm061107l
• 作为产物：
  描述：

  在 乙酸铵 、 碳酸氢钠 作用下， 以 异丙醇 为溶剂， 反应 60.0h， 生成 amino-(2-chloropyridin-3-yl)methylcyanamide
  参考文献：
  名称：

  Evolution of a Highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor

  摘要：

  Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well understood. In order to evaluate the therapeutic utility of inhibiting Tie-2 signaling, we developed a series of potent and orally bioavailable small molecule Tie-2 kinase inhibitors with selectivity over other kinases, especially those that are believed to be important for tumor angiogenesis. Our earlier work provided pyridinyl pyrimidine 6 as a potent, nonselective Tie-2 inhibitor that was designed on the basis of X-ray cocrystal structures of KDR inhibitors 34 (triazine) and 35 (nicotinamide). Lead optimization resulted in pyridinyl triazine 63, which exhibited > 30-fold selectivity over a panel of kinases, good oral exposure, and in vivo inhibition of Tie-2 phosphorylation.

  DOI：

  10.1021/jm061107l

文献信息

• Kinase inhibitors
  申请人：Amgen Inc.

  公开号：US20040116388A1

  公开（公告）日：2004-06-17

  The invention relates to inhibitors of enzymes that bind to ATP or GTP and/or catalyze phosphoryl transfer, compositions comprising the inhibitors, and methods of using the inhibitors and inhibitor compositions. The inhibitors and compositions comprising them are useful for treating disease or disease symptoms. The invention also provides for methods of making phosphoryl transferase inhibitor compounds, methods of inhibiting phosphoryl transferase activity, and methods for treating disease or disease symptoms.

  这项发明涉及与ATP或GTP结合并/或催化磷酸转移的酶的抑制剂，包括这些抑制剂的组合物，以及使用这些抑制剂和抑制剂组合物的方法。这些抑制剂和包含它们的组合物对治疗疾病或疾病症状是有用的。该发明还提供了制备磷酸转移酶抑制剂化合物的方法，抑制磷酸转移酶活性的方法，以及治疗疾病或疾病症状的方法。
• [EN] NITROGENATED HETEROCYCLIC DERIVATIVES AS PROTEIN KINASE MODULATORS AND USE FOR THE TREATMENT OF ANGIOGENESIS AND CANCER<br/>[FR] MODULATEURS DE PROTEINES KINASES ET PROCEDE D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2005113494A3

  公开（公告）日：2006-03-16