1,4,6-三甲基-2-氧代-1,2-二氢-3-吡啶甲腈 | 64038-03-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 1,4,6-三甲基-2-氧代-1,2-二氢-3-吡啶甲腈
• 英文名称: 1,4,6-trimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
• 英文别名: 1-methyl-4,6-dimethyl-3-cyano-2-pyridone；3-cyano-1,4,6-trimethylpyridin-2(1H)-one；N-methyl-4,6-dimethyl-3-cyano-2-pyridone；3-cyano-1,4,6-trimethyl-2-pyridone；1,4,6-trimethyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile；1,4,6-Trimethyl-2-oxo-1,2-dihydro-pyridin-3-carbonitril；1,4,6-Trimethyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile；1,4,6-trimethyl-2-oxopyridine-3-carbonitrile
• CAS: 64038-03-5
• 化学式: C₉H₁₀N₂O
• mdl: MFCD00829059
• 分子量: 162.191
• InChiKey: YHNFRZWVZUMYEJ-UHFFFAOYSA-N

物化性质

• 熔点：
  202-204°
• 溶解度：
  >24.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  1,4,6-三甲基-2-氧代-1,2-二氢-3-吡啶甲腈 在 ammonium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 18.0h， 生成 5-chloro-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methyl-N-((1,4,6-trimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide
  参考文献：
  名称：

  The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat

  摘要：

  Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation. Enhancer of Zeste homologue 2 (EZH2) methylates histone 3 at lysine 27 (H3K27) and abnormal methylation of this site is found in many cancers. Tazemetostat, an EHZ2 inhibitor in clinical development, has shown activity in both preclinical models of cancer as well as in patients with lymphoma or INI1-deficient solid tumors. Herein we report the structure activity relationships from identification of an initial hit in a high-throughput screen through selection of tazemetostat for clinical development. The importance of several methyl groups to the potency of the inhibitors is highlighted as well as the importance of balancing pharmacokinetic properties with potency.

  DOI：

  10.1021/acs.jmedchem.5b01501
• 作为产物：
  描述：

  1,4,6,6-tetramethyl-2-oxo-1,2,5,6-tetrahydro-pyridine-3-carbonitrile 生成 1,4,6-三甲基-2-氧代-1,2-二氢-3-吡啶甲腈
  参考文献：
  名称：

  Guareschi; Grande, Chemisches Zentralblatt, 1899, vol. 70, # II, p. 440

  摘要：

  DOI：

文献信息

• Methyl Orthocarboxylates as Methylating Agents of Heterocycles
  作者：Yves L. Janin、Christiane Huel、Geneviève Flad、Sylvie Thirot

  DOI：10.1002/1099-0690(200206)2002:11<1763::aid-ejoc1763>3.0.co;2-q

  日期：2002.6

  rearrangement into, mostly, 1-methylpyridin-2(1H)-one was studied. The new techniques described here (methanol trapping with 4 A molecular sieves and Lewis acid-catalyzed reaction) greatly increase the potential of trimethyl orthocarboxylates. These reagents can be considered as possible alternatives to the dimethyl formamide-producing N,N-dimethylformamide dimethyl acetal and may sometimes be attractive

  作为经典甲基化方法的替代方法，研究了原羧酸三甲酯或 N，N-二甲基甲酰胺二甲基缩醛与各种羟基化杂环之间发生的甲基化反应，涉及内酰胺-内酰胺互变异构平衡。相应的 O-甲基化或 N-甲基化化合物在许多情况下被分离出来，反应的区域选择性有时会跟随，有时与使用标准甲基化方法的相应结果不同。在这项工作的过程中，注意到了以前未报告的影响。在一种情况下，使用甲苯作为反应溶剂会产生更多的 N-甲基化物质。在其他情况下，试剂的空间体积和/或稳定性的影响（原甲酸酯与原乙酸酯或 N,N-二甲基甲酰胺二甲基缩醛与 其乙酰胺同系物）也被注意到。有时可以避免不需要的甲酰化反应，并且在较少情况下观察到 O-甲基化物质的增加。先前未报道的 1-dimethoxymethylpyridin-2(1H)-one 被表征，并研究了其酸催化重排成，主要是 1-methylpyridin-2(1H)-one。这里描述的新技术（用 4
• 1-Alkylpyrid-2-one
  申请人：Rohm and Haas Company

  公开号：US04038065A1

  公开（公告）日：1977-07-26

  Novel compounds belonging to the class of 3-carboxy (or the physiologically acceptable salts thereof), 3-carbalkoxy, and 3-carbamoyl-1-alkyl-4,6-disubstituted pyrid-2-ones. These compounds possess biological activity and in particular are gametocides and plant growth regulators. Novel 3-cyano-1-alkyl-4,6-disubstituted pyrid-2-ones are also disclosed as intermediates.

  属于3-羧基（或其生理上可接受的盐），3-羧酰氧基和3-羰基-1-烷基-4,6-二取代吡啶-2-酮类的新化合物。这些化合物具有生物活性，特别是作为配子杀灭剂和植物生长调节剂。还披露了新的3-氰基-1-烷基-4,6-二取代吡啶-2-酮作为中间体。
• 1-Alkylpyrid-2-ones
  申请人：Rohm and Haas Company

  公开号：US04108630A1

  公开（公告）日：1978-08-22

  Novel compounds belonging to the class of 3-carboxy (or the physiologically acceptable salts thereof), 3-carbalkoxy, and 3-carbamoyl-1-alkyl-4,6-disubstituted pyrid-2-ones. These compounds possess biological activity and in particular are gametocides and plant growth regulators. Novel 3-cyano-1-alkyl-4,6-disubstituted pyrid-2-ones are also disclosed as intermediates.

  这是一段关于新型化合物的描述，属于3-羧基（或其生理可接受的盐）、3-羧基烷氧基、3-羧酰胺-1-烷基-4,6-二取代吡啶-2-酮类。这些化合物具有生物活性，特别是作为杀虫剂和植物生长调节剂。此外，还揭示了新型3-氰基-1-烷基-4,6-二取代吡啶-2-酮作为中间体。
• Substituted Benzene Compounds
  申请人：Kuntz Kevin Wayne

  公开号：US20140142083A1

  公开（公告）日：2014-05-22

  The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

  本发明涉及取代苯化合物。本发明还涉及含有这些化合物的制药组合物以及通过将这些化合物和制药组合物用于需要治疗的受试者的方法来治疗癌症。本发明还涉及将这些化合物用于研究或其他非治疗目的的使用。
• SUBSTITUTED BENZENE COMPOUNDS
  申请人：EPIZYME, INC.

  公开号：US20150284370A1

  公开（公告）日：2015-10-08

  The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

  本发明涉及取代苯基化合物。本发明还涉及含有这些化合物的制药组合物，以及通过将这些化合物和制药组合物用于需要此类治疗的受试者来治疗癌症的方法。本发明还涉及将这些化合物用于研究或其他非治疗目的的用途。