6-{[6-(trifluoromethyl)pyrazin-2-yl]amino}-3,4-dihydroquinolin-2(1H)-one | 1579950-45-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-{[6-(trifluoromethyl)pyrazin-2-yl]amino}-3,4-dihydroquinolin-2(1H)-one
• 英文别名: 6-[[6-(trifluoromethyl)pyrazin-2-yl]amino]-3,4-dihydro-1H-quinolin-2-one
• CAS: 1579950-45-0
• 化学式: C₁₄H₁₁F₃N₄O
• 分子量: 308.263
• InChiKey: HWTUCDIANCDRFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  66.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-溴-1,2,3,4-四氢-2-喹啉酮 、 6-(三氟甲基)吡嗪-2-胺 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 sodium t-butanolate 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 甲苯 为溶剂， 反应 3.5h， 以21%的产率得到6-{[6-(trifluoromethyl)pyrazin-2-yl]amino}-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  Kinesin Spindle Protein Inhibitors with Diaryl Amine Scaffolds: Crystal Packing Analysis for Improved Aqueous Solubility

  摘要：

  Diaryl amine derivatives have been designed and synthesized as novel kinesin spindle protein (KSP) inhibitors based on planar carbazole-type KSP inhibitors with poor aqueous solubility. The new generation of inhibitors was found to show comparable inhibitory activity and high selectivity for KSP, and this was accompanied with improved solubility. Kinetic analysis and molecular modeling studies suggested that these inhibitors work in an ATP-competitive manner via binding to the secondary allosteric site formed by alpha 4 and alpha 6 helices of KSP. Comparative structural investigations on a series of compounds revealed that the higher solubility of diaryl amine-type inhibitors was attributed to fewer van der Waals interactions in the crystal packing and the hydrogen-bond acceptor nitrogen of the aniline moiety for favorable solvation.

  DOI：

  10.1021/ml500016j

文献信息

• [EN] Eg5 INHIBITOR<br/>[FR] INHIBITEUR D'Eg5
  申请人：UNIV KYOTO

  公开号：WO2014174745A1

  公开（公告）日：2014-10-30

  　本発明の水溶性多環性化合物又はその薬理学的に許容される塩は、従来のＥｇ５（ＫＳＰ：キネシンスピンドルタンパク質）阻害剤と比較して、水性溶媒に対して大きな溶解度を有し、且つ従来のＥｇ５阻害剤と同等若しくはそれ以上のＥｇ５阻害活性を有する。さらに、これらの特性により種々の癌細胞に対し顕著な成長阻害活性を有し、癌等の治療に非常に有効である。
• Kinesin Spindle Protein Inhibitors with Diaryl Amine Scaffolds: Crystal Packing Analysis for Improved Aqueous Solubility
  作者：Tomoki Takeuchi、Shinya Oishi、Masato Kaneda、Hiroaki Ohno、Shinya Nakamura、Isao Nakanishi、Masayoshi Yamane、Jun-ichi Sawada、Akira Asai、Nobutaka Fujii

  DOI：10.1021/ml500016j

  日期：2014.5.8

  Diaryl amine derivatives have been designed and synthesized as novel kinesin spindle protein (KSP) inhibitors based on planar carbazole-type KSP inhibitors with poor aqueous solubility. The new generation of inhibitors was found to show comparable inhibitory activity and high selectivity for KSP, and this was accompanied with improved solubility. Kinetic analysis and molecular modeling studies suggested that these inhibitors work in an ATP-competitive manner via binding to the secondary allosteric site formed by alpha 4 and alpha 6 helices of KSP. Comparative structural investigations on a series of compounds revealed that the higher solubility of diaryl amine-type inhibitors was attributed to fewer van der Waals interactions in the crystal packing and the hydrogen-bond acceptor nitrogen of the aniline moiety for favorable solvation.