NSC 380849 | 127033-30-1

• 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: NSC 380849
• 英文别名: (E)-7-chloro-2-styrylquinazolin-4(3H)-one；7-chloro-2-styrylquinazolin-4(3H)-one；7-chloro-2-[(E)-2-phenylethenyl]-3H-quinazolin-4-one
• CAS: 127033-30-1
• 化学式: C₁₆H₁₁ClN₂O
• 分子量: 282.729
• InChiKey: CNTRVPIASDCUMI-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  NSC 380849 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 8.0h， 以46%的产率得到4,7-dichloro-2-[(E)-2-phenylethenyl]quinazoline
  参考文献：
  名称：

  基于结构的目标特异性筛选导致小分子CaMKII抑制剂。

  摘要：

  靶标特异性评分方法更常用于在对接至目标靶标的化合物中鉴定小分子抑制剂。这些方法中出现的最佳候选物很少经过蛋白质家族的活性和特异性测试。在这项研究中，我们将化学文库停靠在CaMKIIδ（Ca2 + /钙调蛋白（CaM）依赖性蛋白激酶（CaMK）家族的成员）中，并使用支持向量机SPecific（SVMSP）重新评估了所得的蛋白质-化合物结构。我们之前开发的针对特定目标的方法。在35个候选候选人中，确定了3个匹配项，例如喹唑啉化合物1（KIN-1； N4- [7-氯-2-[（E）-苯乙烯基]喹唑啉-4-基] -N1，N1-二乙基戊烷- 1,4-二胺），发现在单位数微摩尔IC50时抑制CaMKIIδ激酶活性。通过分析1的类似物（KIN-236; N4- [7-氯-2-[（E）-2-（2-氯-4,5-二甲氧基苯基）乙烯基]喹唑啉- 4-基] -N1，N1-N1-二乙基戊烷-1,4-二胺）和命中化合物2的类似物（KIN-15;

  DOI：

  10.1002/cmdc.201600636
• 作为产物：
  描述：

  4-Chloro-2-(3-phenyl-acryloylamino)-benzoic acid 在 formamide 作用下， 反应 6.0h， 生成 NSC 380849
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization

  摘要：

  A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.

  DOI：

  10.1021/jm00168a029

文献信息

• Rapid assembly of quinazolinone scaffold via copper-catalyzed tandem reaction of 2-bromobenzamides with aldehydes and aqueous ammonia: application to the synthesis of the alkaloid tryptanthrin
  作者：Shenghai Guo、Yan Li、Li Tao、Wenwen Zhang、Xuesen Fan

  DOI：10.1039/c4ra10799c

  日期：——

  procedure for the preparation of 2-substituted and 2,3-disubstituted quinazolinones was achieved through copper-catalyzed tandem reaction of 2-bromobenzamides with aldehydes and aqueous ammonia under air. Control experimental results indicated that this tandem reaction is triggered by a copper-catalyzed direct amination of 2-bromobenzamides with aqueous ammonia, followed by cyclocondensation and oxidative

  通过2-溴苯甲酰胺与醛和氨水在空气中的铜催化串联反应，实现了制备2-取代的和2,3-二取代的喹唑啉酮的有效而实用的程序。对照实验结果表明，该串联反应是通过铜催化的2-溴苯甲酰胺与氨水的直接胺化反应，然后进行环缩合和氧化芳构化而引发的。作为一种应用，这种新颖的方法为生物碱类胰蛋白酶的合成提供了一种简洁实用的一锅法。
• JIANG, J. B.;HESSON, D. P.;DUSAK, B. A.;DEXTER, D. L.;KANG, G. J.;HAMEL, +, J. MED. CHEM., 33,(1990) N, C. 1721-1728
  作者：JIANG, J. B.、HESSON, D. P.、DUSAK, B. A.、DEXTER, D. L.、KANG, G. J.、HAMEL, +

  DOI：——

  日期：——
• Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization
  作者：Jack B. Jiang、D. P. Hesson、B. A. Dusak、D. L. Dexter、G. J. Kang、E. Hamel

  DOI：10.1021/jm00168a029

  日期：1990.6

  A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.
• Structure-Based Target-Specific Screening Leads to Small-Molecule CaMKII Inhibitors
  作者：David Xu、Liwei Li、Donghui Zhou、Degang Liu、Andy Hudmon、Samy O. Meroueh

  DOI：10.1002/cmdc.201600636

  日期：2017.5.9

  Target-specific scoring methods are more commonly used to identify small-molecule inhibitors among compounds docked to a target of interest. Top candidates that emerge from these methods have rarely been tested for activity and specificity across a family of proteins. In this study we docked a chemical library into CaMKIIδ, a member of the Ca2+ /calmodulin (CaM)-dependent protein kinase (CaMK) family

  靶标特异性评分方法更常用于在对接至目标靶标的化合物中鉴定小分子抑制剂。这些方法中出现的最佳候选物很少经过蛋白质家族的活性和特异性测试。在这项研究中，我们将化学文库停靠在CaMKIIδ（Ca2 + /钙调蛋白（CaM）依赖性蛋白激酶（CaMK）家族的成员）中，并使用支持向量机SPecific（SVMSP）重新评估了所得的蛋白质-化合物结构。我们之前开发的针对特定目标的方法。在35个候选候选人中，确定了3个匹配项，例如喹唑啉化合物1（KIN-1； N4- [7-氯-2-[（E）-苯乙烯基]喹唑啉-4-基] -N1，N1-二乙基戊烷- 1,4-二胺），发现在单位数微摩尔IC50时抑制CaMKIIδ激酶活性。通过分析1的类似物（KIN-236; N4- [7-氯-2-[（E）-2-（2-氯-4,5-二甲氧基苯基）乙烯基]喹唑啉- 4-基] -N1，N1-N1-二乙基戊烷-1,4-二胺）和命中化合物2的类似物（KIN-15;