N-methyl-2-(4-(3,4,5-trimethoxyphenylamino)-1,3,5-triazin-2-ylamino)benzamide | 1448791-29-4

• 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: N-methyl-2-(4-(3,4,5-trimethoxyphenylamino)-1,3,5-triazin-2-ylamino)benzamide
• 英文别名: N-Methyl-2-[[4-[(3,4,5-Trimethoxyphenyl)amino]-1,3,5-Triazin-2-Yl]amino]benzamide；N-methyl-2-[[4-(3,4,5-trimethoxyanilino)-1,3,5-triazin-2-yl]amino]benzamide
• CAS: 1448791-29-4
• 化学式: C₂₀H₂₂N₆O₄
• 分子量: 410.432
• InChiKey: UQGQBHYGCQYHMP-UHFFFAOYSA-N

物化性质

• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯胺 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 N-methyl-2-(4-(3,4,5-trimethoxyphenylamino)-1,3,5-triazin-2-ylamino)benzamide
  参考文献：
  名称：

  Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity

  摘要：

  We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAR (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG. X-ray crystallographic analysis of the co-crystal structure for compound 34 revealed that the mode of interaction with the FAR kinase domain is highly similar to that observed in the complex of TAE-226. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.038

文献信息

• FAK inhibitor and drug combination thereof
  申请人：HINOVA PHARMACEUTICALS INC.

  公开号：US20220125788A1

  公开（公告）日：2022-04-28

  A deuterated compound as represented by formula (I) or an optical isomer, a tautomer, a pharmaceutically acceptable salt, a prodrug, a hydrate, or a solvate thereof are presented. Compared with a compound before deuteration, the deuterated compound shows better pharmacokinetics, higher maximum plasma drug concentration, higher exposure, and longer half-life, and has more excellent metabolic performance. The deuterated compound can effectively inhibit FAK activity, and has good application prospect in preparation of FAK inhibitors and/or drugs for treating cancer. In addition, the use of the deuterated compound in combination with an anti-cancer drug (such as a PD-1 inhibitor) can achieve a synergistic effect, thereby significantly improving the tumor suppression effect, and providing a better choice for clinical cancer treatment.

  本发明提供了由公式(I)所表示的氘代化合物或其光学异构体、互变异构体、药学上可接受的盐、前药、水合物或溶剂化物。与氘代化合物之前的化合物相比，氘代化合物表现出更好的药代动力学、更高的最大血浆药物浓度、更高的曝光度和更长的半衰期，并具有更出色的代谢性能。氘代化合物可以有效地抑制FAK活性，在制备FAK抑制剂和/或用于治疗癌症的药物方面具有良好的应用前景。此外，将氘代化合物与抗癌药物（如PD-1抑制剂）联合使用可以实现协同作用，从而显著提高肿瘤抑制效果，为临床癌症治疗提供更好的选择。
• Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity
  作者：Pascal Dao、Rafika Jarray、Johanne Le Coq、Daniel Lietha、Ali Loukaci、Yves Lepelletier、Réda Hadj-Slimane、Christiane Garbay、Françoise Raynaud、Huixiong Chen

  DOI：10.1016/j.bmcl.2013.06.038

  日期：2013.8

  We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAR (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG. X-ray crystallographic analysis of the co-crystal structure for compound 34 revealed that the mode of interaction with the FAR kinase domain is highly similar to that observed in the complex of TAE-226. (C) 2013 Elsevier Ltd. All rights reserved.