N-(5-nitro-2-(4-methylpiperazin-1-yl)phenyl)acetamide | 5991-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(5-nitro-2-(4-methylpiperazin-1-yl)phenyl)acetamide
• 英文别名: 2-(4-Methylpiperazin-1-yl)-5-nitroacetanilid；N-[2-(4-methyl-piperazin-1-yl)-5-nitro-phenyl]-acetamide；N-[2-(4-methylpiperazin-1-yl)-5-nitrophenyl]acetamide
• CAS: 5991-09-3
• 化学式: C₁₃H₁₈N₄O₃
• 分子量: 278.311
• InChiKey: FSQBTKZGKQMDMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(5-nitro-2-(4-methylpiperazin-1-yl)phenyl)acetamide 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以0.27 g的产率得到N-(5-amino-2-(4-methylpiperazin-1-yl)phenyl)acetamide
  参考文献：
  名称：

  Potent and Selective CK2 Kinase Inhibitors with Effects on Wnt Pathway Signaling in Vivo

  摘要：

  The Wnt pathway is an evolutionarily conserved and tightly regulated signaling network with important roles in embryonic development and adult tissue regeneration. Impaired Wnt pathway regulation, arising from mutations in Wnt signaling components, such as Axin, APC, and beta-catenin, results in uncontrolled cell growth and triggers oncogenesis. To explore the reported link between CK2 kinase activity and Wnt pathway signaling, we sought to identify a potent, selective inhibitor of CK2 suitable for proof of concept studies in vivo. Starting from a pyrazolo[1,5-a]pyrimidine lead (2), we identified compound 7h, a potent CK2 inhibitor with picomolar affinity that is highly selectivity against other kinase family enzymes and inhibits Wnt pathway signaling (IC50 = 50 nM) in DLD-1 cells. In addition, compound 7h has physicochemical properties that are suitable for formulation as an intravenous solution, has demonstrated good pharmacokinetics in preclinical species, and exhibits a high level of activity as a monotherapy in HCT-116 and SW-620 xenografts.

  DOI：

  10.1021/acsmedchemlett.5b00452
• 作为产物：
  描述：

  2-氟-5-硝基苯胺 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-(5-nitro-2-(4-methylpiperazin-1-yl)phenyl)acetamide
  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

• DIAMINO HETEROCYCLIC CARBOXAMIDE COMPOUND
  申请人：Shimada Itsuro

  公开号：US20120040968A1

  公开（公告）日：2012-02-16

  Provided is a compound useful as an inhibitor against the kinase activity of EML4-ALK fusion protein. As a result of intensive and extensive studies on compounds having inhibitory activity against the kinase activity of EML4-ALK fusion protein, the present inventors found that the diamino heterocyclic carboxamide compounds of the present invention had inhibitory activity against the kinase activity of EML4-ALK fusion protein. By this finding, the present invention was completed. The compounds of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, such as lung cancer, non-small cell lung cancer, and small cell lung cancer.

  提供的是一种化合物，可作为抑制EML4-ALK融合蛋白激酶活性的抑制剂。通过对具有抑制EML4-ALK融合蛋白激酶活性的化合物进行深入广泛的研究，本发明人发现本发明的二氨基杂环羧酰胺化合物对EML4-ALK融合蛋白激酶活性具有抑制作用。通过这一发现，完成了本发明。本发明的化合物可用作预防和/或治疗癌症，如肺癌、非小细胞肺癌和小细胞肺癌的药物组合物。
• Diamino heterocyclic carboxamide compound
  申请人：Shimada Itsuro

  公开号：US08969336B2

  公开（公告）日：2015-03-03

  Provided is a compound useful as an inhibitor against the kinase activity of EML4-ALK fusion protein. As a result of intensive and extensive studies on compounds having inhibitory activity against the kinase activity of EML4-ALK fusion protein, the present inventors found that the diamino heterocyclic carboxamide compounds of the present invention had inhibitory activity against the kinase activity of EML4-ALK fusion protein. By this finding, the present invention was completed. The compounds of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, such as lung cancer, non-small cell lung cancer, and small cell lung cancer.

  提供的是一种化合物，可作为抑制EML4-ALK融合蛋白激酶活性的抑制剂。通过对具有抑制EML4-ALK融合蛋白激酶活性的化合物进行深入和广泛的研究，本发明人发现本发明的二氨基杂环羧酰胺化合物具有抑制EML4-ALK融合蛋白激酶活性的作用。通过这一发现，本发明得以完成。本发明的化合物可用作预防和/或治疗癌症，如肺癌、非小细胞肺癌和小细胞肺癌的药物组合物。
• US8969336B2
  申请人：——

  公开号：US8969336B2

  公开（公告）日：2015-03-03
• US9487491B2
  申请人：——

  公开号：US9487491B2

  公开（公告）日：2016-11-08
• 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).