3-cyano-4,6-dimethyl-1-phenyl-2(1H)-pyridone | 53475-36-8

• 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
• 英文名称: 3-cyano-4,6-dimethyl-1-phenyl-2(1H)-pyridone
• 英文别名: N-phenyl-4,6-dimethyl-3-cyano-2-pyridone；4,6-dimethyl-2-oxo-1-phenyl-1,2-dihydro-pyridine-3-carbonitrile；4,6-Dimethyl-2-oxo-1-phenyl-1,2-dihydro-pyridin-3-carbonitril；1,2-Dihydro-4,6-dimethyl-2-oxo-1-phenyl-3-pyridinecarbonitrile；4,6-dimethyl-2-oxo-1-phenylpyridine-3-carbonitrile
• CAS: 53475-36-8
• 化学式: C₁₄H₁₂N₂O
• 分子量: 224.262
• InChiKey: VCOYKJHQTUSEFG-UHFFFAOYSA-N

物化性质

• 熔点：
  255 °C(Solv: cyclohexane (110-82-7))
• 沸点：
  370.6±35.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-cyano-4,6-dimethyl-1-phenyl-2(1H)-pyridone 在 硫酸 作用下， 生成 4,6-dimethyl-2-oxo-1-phenyl-1,2-dihydro-pyridine-3-carboxylic acid amide
  参考文献：
  名称：

  Ried; Schleimer, Justus Liebigs Annalen der Chemie, 1959, vol. 626, p. 106,112

  摘要：

  DOI：
• 作为产物：
  描述：

  苯胺 在 甲醇 、 乙醚 、 二乙胺 作用下， 生成 3-cyano-4,6-dimethyl-1-phenyl-2(1H)-pyridone
  参考文献：
  名称：

  Ried; Schleimer, Justus Liebigs Annalen der Chemie, 1959, vol. 626, p. 106,112

  摘要：

  DOI：

文献信息

• Discovery of 8-Amino-Substituted 2-Phenyl-2,7-Naphthyridinone Derivatives as New c-Kit/VEGFR-2 Kinase Inhibitors
  作者：Haiyan Sun、Linsheng Zhuo、Huan Dong、Wei Huang、Nengfang She

  DOI：10.3390/molecules24244461

  日期：——

  scaffold has been proposed as a novel lead structure of MET inhibitors by our group. To broaden the application of this new scaffold, a series of 8-amino-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one derivatives were designed and synthesized. Preliminary biological screening resulted in the discovery of a new lead of c-Kit and VEGFR-2 kinase inhibitors. Compound 9k exhibited excellent c-Kit inhibitory activity

  我们小组已提出 2,7-萘啶酮支架作为 MET 抑制剂的新型先导结构。为了扩大这种新支架的应用，设计并合成了一系列 8-氨基取代的 2-苯基-2,7-萘啶-1(2H)-one 衍生物。初步生物筛选导致发现了 c-Kit 和 VEGFR-2 激酶抑制剂的新先导。化合物9k表现出优异的c-Kit抑制活性，IC50值为8.5nM，即比化合物3(IC50为329.6nM)强38.8倍。此外，化合物10l 和10r 表现出良好的VEGFR-2 抑制活性，IC50 值分别为56.5 和31.7 nM，即它们比化合物3（IC50 为279.9 nM）强5.0-8.8 倍。分子对接实验进一步深入了解新先导化合物与 c-Kit 和 VEGFR-2 激酶的结合相互作用。在这项研究中，8-氨基取代的 2-苯基-2,7-naphthyridin-1(2H)-one 支架被确定为 c-Kit 和 VEGFR-2 激酶抑制剂的新先导结构。
• 2,7-naphthyridinone-based MET kinase inhibitors: A promising novel scaffold for antitumor drug development
  作者：Lin-Sheng Zhuo、Hong-Chuang Xu、Ming-Shu Wang、Xing-E. Zhao、Zhi-Hui Ming、Xiao-Lei Zhu、Wei Huang、Guang-Fu Yang

  DOI：10.1016/j.ejmech.2019.06.033

  日期：2019.9

  As part of our effort to develop new molecular targeted antitumor drug, a novel 2,7-naphthyridone-based MET kinase inhibitor, 8-((4-((2-amino-3-chloropyridin-4-yl)oxy)- 3-fluorophenyl)amino)-2-(4-fluorophenyl)-2,7-naphthyridin-1(2H)-one (13f), was identified. Knowledge of the binding mode of BMS-777607 in MET led to the design of new inhibitors that utilize novel 2,7-naphthyridone scaffold to conformationally restrain the key pharmacophoric groups (block C). Detailed SAR studies resulted in the discovery of a new MET inhibitor 13f, displaying favorable in vitro potency and oral bioavailability. More importantly, 13f exhibited excellent in vivo efficacy (tumor growth inhibition/TGI of 114% and 95% in 50 mg/kg, respectively) both in the U-87 MG and HT-29 xenograft models. The favorable drug-likeness of 13f indicated that 2,7-naphthyridinone may be used a promising novel scaffold for antitumor drug development. The preclinical studies of 13f are under way.
• Synthesis of N‐Substituted 4,6‐Dimethyl‐3‐cyano‐2‐pyridones Under Microwave Irradiation
  作者：Dušan Mijin、Aleksandar Marinković

  DOI：10.1080/00397910500334421

  日期：2006.2.1

  N-substituted 4,6-dimethyl-3-cyano-2-pyridones have been prepared from acetylacetone, N-substituted cyanoacetamide, and pyperidine as catalyst under microwave irradiation without solvent. The rapid and simple method produced pure products in high yields.
• Ionic Liquid Catalyzed 4,6-Disubstituted-3-Cyano-2-Pyridone Synthesis Under Solvent-Free Conditions
  作者：Sunil S. Chavan、Mariam S. Degani

  DOI：10.1007/s10562-011-0700-5

  日期：2011.11

  A green protocol for the synthesis of 4,6-disubstituted-3-cyano-2-pyridones from cyanoacetamides and 1,3-dicarbonyl compounds or chalcones using guanidine based ionic liquid as catalyst has been developed. In solvent-free conditions at 30 A degrees C, [TMG][Lac] (1,1,3,3-tetramethylguanidine lactate) was found to have the highest catalytic activity among the ionic liquids including [TMG][Ac] (1,1,3,3-tetramethylguanidine acetate), [TMG][Pr] (1,1,3,3-tetramethylguanidine propionate), [TMG][n-Bu] (1,1,3,3-tetramethylguanidine n-butyrate) and [TMG][TFA] (1,1,3,3-tetramethylguanidine trifluoroacetate). The catalyst was recovered and recycled several times without significant loss of catalytic activity.
• Alberola, Angel; Andres, Celia; Ortega, Alfonso Gonzalez, Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 709 - 713
  作者：Alberola, Angel、Andres, Celia、Ortega, Alfonso Gonzalez、Pedrosa, Rafael、Vicente, Martina

  DOI：——

  日期：——