N1,N4-bis(3-((4-((7-chloroquinolin-4-yl)amino)butyl)carbamoyl)-5-cyanophenyl)terephthalamide | 1234676-76-6

• 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: N1,N4-bis(3-((4-((7-chloroquinolin-4-yl)amino)butyl)carbamoyl)-5-cyanophenyl)terephthalamide
• CAS: 1234676-76-6
• 化学式: C₅₀H₄₂Cl₂N₁₀O₄
• 分子量: 917.854
• InChiKey: XCMPUJVCXVAPKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.58
• 重原子数：
  66.0
• 可旋转键数：
  18.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  213.82
• 氢给体数：
  6.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N1,N4-bis(3-((4-((7-chloroquinolin-4-yl)amino)butyl)carbamoyl)-5-cyanophenyl)terephthalamide 、 乙二胺 在 sodium hydrogen sulfide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 生成 1-N,4-N-bis[3-[4-[(7-chloroquinolin-4-yl)amino]butylcarbamoyl]-5-(4,5-dihydro-1H-imidazol-2-yl)phenyl]benzene-1,4-dicarboxamide
  参考文献：
  名称：

  Pharmacophore Refinement Guides the Design of Nanomolar-Range Botulinum Neurotoxin Serotype A Light Chain Inhibitors

  摘要：

  Botulinum neurotoxins (BoNTs) are the deadliest of microbial toxins. The enzyme's zinc(II) metalloprotease, referred to as the light chain (LC) component, inhibits acetylcholine release into neuromuscular junctions, resulting in the disease botulism. Currently, no therapies counter BoNT poisoning postneuronal intoxication; however it is hypothesized that small molecules may be used to inhibit BoNT LC activity in the neuronal cytosol. Herein, we describe the pharmacophore-based design and chemical synthesis of potent [non-zinc(II) chelating] small molecule (nonpeptidic) inhibitors (SMNPIs) of the BoNT serotype-A LC (the most toxic of the BoNT serotype LCs). Specifically the three-dimensional superimpositions of 2-[4-(4-amidinephenoxy)-phenyl]indole-6-amidine-based SMNPI regionisomers [K-i = 0.600 mu M (+/-0.100 mu M)], with a novel lead bis-[3-amide-5-(imidazolino) phenyl]terephthalamide (BAIPT)-based SMNPI [K-i = 8.52 mu M (+/-0.53 mu M)], resulted in a refined four zone pharmacophore. The refined model guided the design of BAIPT-based SMNPIs possessing K-i values = 0.572 (+/-0.041 mu M) and 0.900 mu M (0.078 mu M).

  DOI：

  10.1021/ml100056v
• 作为产物：
  描述：

  5,5'-(terephthaloylbis(azanediyl))bis(3-cyanobenzoic acid) 、 4-(4-氨基丁基)氨基-7-氯喹啉 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 24.0h， 以94%的产率得到N1,N4-bis(3-((4-((7-chloroquinolin-4-yl)amino)butyl)carbamoyl)-5-cyanophenyl)terephthalamide
  参考文献：
  名称：

  Pharmacophore Refinement Guides the Design of Nanomolar-Range Botulinum Neurotoxin Serotype A Light Chain Inhibitors

  摘要：

  Botulinum neurotoxins (BoNTs) are the deadliest of microbial toxins. The enzyme's zinc(II) metalloprotease, referred to as the light chain (LC) component, inhibits acetylcholine release into neuromuscular junctions, resulting in the disease botulism. Currently, no therapies counter BoNT poisoning postneuronal intoxication; however it is hypothesized that small molecules may be used to inhibit BoNT LC activity in the neuronal cytosol. Herein, we describe the pharmacophore-based design and chemical synthesis of potent [non-zinc(II) chelating] small molecule (nonpeptidic) inhibitors (SMNPIs) of the BoNT serotype-A LC (the most toxic of the BoNT serotype LCs). Specifically the three-dimensional superimpositions of 2-[4-(4-amidinephenoxy)-phenyl]indole-6-amidine-based SMNPI regionisomers [K-i = 0.600 mu M (+/-0.100 mu M)], with a novel lead bis-[3-amide-5-(imidazolino) phenyl]terephthalamide (BAIPT)-based SMNPI [K-i = 8.52 mu M (+/-0.53 mu M)], resulted in a refined four zone pharmacophore. The refined model guided the design of BAIPT-based SMNPIs possessing K-i values = 0.572 (+/-0.041 mu M) and 0.900 mu M (0.078 mu M).

  DOI：

  10.1021/ml100056v