4-(4-amino-5-cyano-6-ethoxypyridin-2-ylamino)benzamide | 1206167-73-8

• 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: 4-(4-amino-5-cyano-6-ethoxypyridin-2-ylamino)benzamide
• 英文别名: 4-[(4-Amino-5-Cyano-6-Ethoxypyridin-2-Yl)amino]benzamide
• CAS: 1206167-73-8
• 化学式: C₁₅H₁₅N₅O₂
• 分子量: 297.316
• InChiKey: JUNWGTQNFTURHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  trifluoromethanesulfonic acid 4-amino-5-cyano-6-ethoxypyridin-2-yl ester 在 氨 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 4-(4-amino-5-cyano-6-ethoxypyridin-2-ylamino)benzamide
  参考文献：
  名称：

  Diaminopyridine-Based Potent and Selective Mps1 Kinase Inhibitors Binding to an Unusual Flipped-Peptide Conformation

  摘要：

  Monopolar spindle 1 (Mps1) is an attractive cancer drug target due to the important role that it plays in centrosome duplication, the spindle assembly checkpoint, and the maintenance of chromosomal stability. A design based on JNK inhibitors with an aminopyridine scaffold and subsequent modifications identified diaminopyridine 9 with an IC50 of 37 nM. The X-ray structure of 9 revealed that the Cys604 carbonyl group of the hinge region flips to form a hydrogen bond with the aniline NH group in 9. Further optimization of 9 led to 12 with improved cellular activity, suitable pharmacokinetic profiles, and good in vivo efficacy in the mouse A549 xenograft model. Moreover, 12 displayed excellent selectivity over 95 kinases, indicating the contribution of its unusual flipped-peptide conformation to its selectivity.

  DOI：

  10.1021/ml3000879

文献信息

• Diaminopyridine-Based Potent and Selective Mps1 Kinase Inhibitors Binding to an Unusual Flipped-Peptide Conformation
  作者：Ken-ichi Kusakabe、Nobuyuki Ide、Yataro Daigo、Takeshi Itoh、Kenichi Higashino、Yousuke Okano、Genta Tadano、Yuki Tachibana、Yuji Sato、Makiko Inoue、Tooru Wada、Motofumi Iguchi、Takayuki Kanazawa、Yukichi Ishioka、Keiji Dohi、Sachie Tagashira、Yasuto Kido、Shingo Sakamoto、Kazuya Yasuo、Masahiro Maeda、Takahiko Yamamoto、Masayo Higaki、Takeshi Endoh、Kazuo Ueda、Takeshi Shiota、Hitoshi Murai、Yusuke Nakamura

  DOI：10.1021/ml3000879

  日期：2012.7.12

  Monopolar spindle 1 (Mps1) is an attractive cancer drug target due to the important role that it plays in centrosome duplication, the spindle assembly checkpoint, and the maintenance of chromosomal stability. A design based on JNK inhibitors with an aminopyridine scaffold and subsequent modifications identified diaminopyridine 9 with an IC50 of 37 nM. The X-ray structure of 9 revealed that the Cys604 carbonyl group of the hinge region flips to form a hydrogen bond with the aniline NH group in 9. Further optimization of 9 led to 12 with improved cellular activity, suitable pharmacokinetic profiles, and good in vivo efficacy in the mouse A549 xenograft model. Moreover, 12 displayed excellent selectivity over 95 kinases, indicating the contribution of its unusual flipped-peptide conformation to its selectivity.