(2R)-N-[4-(10-benzyl-7-thia-2,5,10-triazatricyclo[6.4.0.02,6]dodeca-1(8),3,5-trien-4-yl)phenyl]-2-[[2-(3,5-difluorophenyl)acetyl]amino]-3-tritylsulfanylpropanamide | 1370421-37-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2R)-N-[4-(10-benzyl-7-thia-2,5,10-triazatricyclo[6.4.0.02,6]dodeca-1(8),3,5-trien-4-yl)phenyl]-2-[[2-(3,5-difluorophenyl)acetyl]amino]-3-tritylsulfanylpropanamide
• CAS: 1370421-37-6
• 化学式: C₅₁H₄₃F₂N₅O₂S₂
• 分子量: 860.064
• InChiKey: FVNXSJLREMJKFC-GWHBCOKCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  62
• 可旋转键数：
  14
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R)-N-[4-(10-benzyl-7-thia-2,5,10-triazatricyclo[6.4.0.02,6]dodeca-1(8),3,5-trien-4-yl)phenyl]-2-[[2-(3,5-difluorophenyl)acetyl]amino]-3-tritylsulfanylpropanamide 在 三乙基硅烷 、 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 1.0h， 以40%的产率得到(R)-N-[4-(7-benzyl-5,6,7,8-tetrahydroimidazo[2',1':2,3]thiazolo[5,4-c]pyridin-2-yl)phenyl]-2-[2-(3,5-difluorophenyl)acetamido]-3-sulfanylpropanamide
  参考文献：
  名称：

  Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling

  摘要：

  The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorage-independent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.051
• 作为产物：
  描述：

  3,5-二氟苯乙酸 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 sodium hydroxide 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 32.25h， 生成 (2R)-N-[4-(10-benzyl-7-thia-2,5,10-triazatricyclo[6.4.0.02,6]dodeca-1(8),3,5-trien-4-yl)phenyl]-2-[[2-(3,5-difluorophenyl)acetyl]amino]-3-tritylsulfanylpropanamide
  参考文献：
  名称：

  Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling

  摘要：

  The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorage-independent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.051