1-N,4-N-bis[3-[2-[(7-chloroquinolin-4-yl)amino]ethylcarbamoyl]-5-(4,5-dihydro-1H-imidazol-2-yl)phenyl]benzene-1,4-dicarboxamide | 1234676-67-5

• 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: 1-N,4-N-bis[3-[2-[(7-chloroquinolin-4-yl)amino]ethylcarbamoyl]-5-(4,5-dihydro-1H-imidazol-2-yl)phenyl]benzene-1,4-dicarboxamide
• CAS: 1234676-67-5
• 化学式: C₅₀H₄₄Cl₂N₁₂O₄
• 分子量: 947.883
• InChiKey: BWRAEZBVTGKTRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  68
• 可旋转键数：
  16
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  215
• 氢给体数：
  8
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 1-N,4-N-bis[3-[2-[(7-chloroquinolin-4-yl)amino]ethylcarbamoyl]-5-(4,5-dihydro-1H-imidazol-2-yl)phenyl]benzene-1,4-dicarboxamide 以 乙腈 为溶剂， 反应 0.5h， 以87%的产率得到1-N,4-N-bis[3-[2-[(7-chloroquinolin-4-yl)amino]ethylcarbamoyl]-5-(4,5-dihydro-1H-imidazol-2-yl)phenyl]benzene-1,4-dicarboxamide;methanesulfonic acid
  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：

  N1,N4-bis(3-((2-((7-chloroquinolin-4-yl)amino)ethyl)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-[2-[(7-chloroquinolin-4-yl)amino]ethylcarbamoyl]-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

文献信息

• Pharmacophore Refinement Guides the Design of Nanomolar-Range Botulinum Neurotoxin Serotype A Light Chain Inhibitors
  作者：Jonathan E. Nuss、Yuxiang Dong、Laura M. Wanner、Gordon Ruthel、Peter Wipf、Rick Gussio、Jonathan L. Vennerstrom、Sina Bavari、James C. Burnett

  DOI：10.1021/ml100056v

  日期：2010.10.14

  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).