(E)-N'-((5-chloropyrazolo[1,5-a]pyrimidin-3-yl)methylene)-N,2-dimethylbenzenesulfonohydrazide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-N'-((5-chloropyrazolo[1,5-a]pyrimidin-3-yl)methylene)-N,2-dimethylbenzenesulfonohydrazide
• 英文别名: N-[(E)-(5-chloropyrazolo[1,5-a]pyrimidin-3-yl)methylideneamino]-N,2-dimethylbenzenesulfonamide
• 化学式: C₁₅H₁₄ClN₅O₂S
• 分子量: 363.827
• InChiKey: MVCPWLSPXUGHMG-RQZCQDPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  88.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-氯吡唑并[1,5-a]嘧啶 在 碳酸氢钠 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 19.0h， 生成 (E)-N'-((5-chloropyrazolo[1,5-a]pyrimidin-3-yl)methylene)-N,2-dimethylbenzenesulfonohydrazide
  参考文献：
  名称：

  Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9

  摘要：

  The serine-threonine kinase CDK9 is a target of emerging interest for the development of anti-cancer drugs. There are multiple lines of evidence linking CDK9 activity to cancer, including the essential role this kinase plays in transcriptional regulation through phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. Indeed, inhibition of CDK9 has been shown to result in a reduction of short-lived proteins such as the pro-survival protein Mcl-1 in malignant cells leading to the induction of apoptosis. In this work we report our initial studies towards the discovery of selective CDK9 inhibitors, starting from the known multi-kinase inhibitor PIK-75 which possesses potent CDK9 activity. Our series is based on a pyrazolo[1,5-a] pyrimidine nucleus and, importantly, the resultant lead compound 18b is devoid of the structural liabilities present in PIK-75 and possesses greater selectivity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.035

文献信息

• Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9
  作者：Louisa J. Phillipson、David H. Segal、Tracy L. Nero、Michael W. Parker、Soo San Wan、Melanie de Silva、Mark A. Guthridge、Andrew H. Wei、Christopher J. Burns

  DOI：10.1016/j.bmc.2015.08.035

  日期：2015.10

  The serine-threonine kinase CDK9 is a target of emerging interest for the development of anti-cancer drugs. There are multiple lines of evidence linking CDK9 activity to cancer, including the essential role this kinase plays in transcriptional regulation through phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. Indeed, inhibition of CDK9 has been shown to result in a reduction of short-lived proteins such as the pro-survival protein Mcl-1 in malignant cells leading to the induction of apoptosis. In this work we report our initial studies towards the discovery of selective CDK9 inhibitors, starting from the known multi-kinase inhibitor PIK-75 which possesses potent CDK9 activity. Our series is based on a pyrazolo[1,5-a] pyrimidine nucleus and, importantly, the resultant lead compound 18b is devoid of the structural liabilities present in PIK-75 and possesses greater selectivity. (C) 2015 Elsevier Ltd. All rights reserved.