2-chloro-N-[5-(furan-2-yl)-2-(4-methylpiperazin-1-yl)phenyl]benzamide | 1422390-02-0

• 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: 2-chloro-N-[5-(furan-2-yl)-2-(4-methylpiperazin-1-yl)phenyl]benzamide
• CAS: 1422390-02-0
• 化学式: C₂₂H₂₂ClN₃O₂
• 分子量: 395.889
• InChiKey: NXHDMDGEYLWCRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴-2-氟苯胺 在 吡啶 、 四(三苯基膦)钯 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 2-chloro-N-[5-(furan-2-yl)-2-(4-methylpiperazin-1-yl)phenyl]benzamide
  参考文献：
  名称：

  Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction

  摘要：

  The WD40-repeat protein WDRS plays a critical role in maintaining the integrity of MLL complexes and fully activating their methyltransferase function. MLL complexes, the trithorax-like family of SET1 methyltransferases, catalyze trimethylation of lysine 4 on histone 3, and they have been widely implicated in various cancers. Antagonism of WDR5 and MLL subunit interaction by small molecules has recently been presented as a practical way to inhibit activity of the MLL1 complex, and N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) benzamides were reported as potent and selective antagonists of such an interaction. Here, we describe the protein crystal structure guided optimization of prototypic compound 2 (K-dis = 7 mu M), leading to identification of more potent antagonist 47 (K-dis = 0.3 mu M).

  DOI：

  10.1021/ml300467n

文献信息

• Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction
  作者：Yuri Bolshan、Matthäus Getlik、Ekaterina Kuznetsova、Gregory A. Wasney、Taraneh Hajian、Gennadiy Poda、Kong T. Nguyen、Hong Wu、Ludmila Dombrovski、Aiping Dong、Guillermo Senisterra、Matthieu Schapira、Cheryl H. Arrowsmith、Peter J. Brown、Rima Al-awar、Masoud Vedadi、David Smil

  DOI：10.1021/ml300467n

  日期：2013.3.14

  The WD40-repeat protein WDRS plays a critical role in maintaining the integrity of MLL complexes and fully activating their methyltransferase function. MLL complexes, the trithorax-like family of SET1 methyltransferases, catalyze trimethylation of lysine 4 on histone 3, and they have been widely implicated in various cancers. Antagonism of WDR5 and MLL subunit interaction by small molecules has recently been presented as a practical way to inhibit activity of the MLL1 complex, and N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) benzamides were reported as potent and selective antagonists of such an interaction. Here, we describe the protein crystal structure guided optimization of prototypic compound 2 (K-dis = 7 mu M), leading to identification of more potent antagonist 47 (K-dis = 0.3 mu M).