(R)-2-(4-(3-(dimethylamino)pyrrolidin-1-yl)quinazolin-2-yl)phenol | 1262849-59-1

• 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: (R)-2-(4-(3-(dimethylamino)pyrrolidin-1-yl)quinazolin-2-yl)phenol
• 英文别名: 2-[4-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]quinazolin-2-yl]phenol
• CAS: 1262849-59-1
• 化学式: C₂₀H₂₂N₄O
• 分子量: 334.421
• InChiKey: KRVBCKPGPVGNKQ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-chloro-2-(2-methoxyphenyl)quinazoline 在 三溴化硼 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 24.08h， 生成 (R)-2-(4-(3-(dimethylamino)pyrrolidin-1-yl)quinazolin-2-yl)phenol
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 2-(Quinazolin-2-yl)phenol Inhibitors of Checkpoint Kinase 2

  摘要：

  Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl)phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2-(quinazolin-2-yl)phenol 46 (IC(50) 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of kinases and with promising in vitro ADMET properties. Off-target activity at hERG ion channels shown by the core scaffold was successfully reduced by the addition of peripheral polar substitution. In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533).

  DOI：

  10.1021/jm101150b

文献信息

• Structure-Based Design of Potent and Selective 2-(Quinazolin-2-yl)phenol Inhibitors of Checkpoint Kinase 2
  作者：John J. Caldwell、Emma J. Welsh、Cornelis Matijssen、Victoria E. Anderson、Laurent Antoni、Kathy Boxall、Frederique Urban、Angela Hayes、Florence I. Raynaud、Laurent J. M. Rigoreau、Tony Raynham、G. Wynne Aherne、Laurence H. Pearl、Antony W. Oliver、Michelle D. Garrett、Ian Collins

  DOI：10.1021/jm101150b

  日期：2011.1.27

  Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl)phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2-(quinazolin-2-yl)phenol 46 (IC(50) 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of kinases and with promising in vitro ADMET properties. Off-target activity at hERG ion channels shown by the core scaffold was successfully reduced by the addition of peripheral polar substitution. In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533).