(S)-N-(3,4-dimethylpent-1-yn-3-yl)-1-(quinolin-6-yl)methanimine | 1029431-41-1

• 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: (S)-N-(3,4-dimethylpent-1-yn-3-yl)-1-(quinolin-6-yl)methanimine
• CAS: 1029431-41-1
• 化学式: C₁₇H₁₈N₂
• 分子量: 250.343
• InChiKey: SDZJQONYDZLVSO-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  25.25
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (S)-N-(3,4-dimethylpent-1-yn-3-yl)-1-(quinolin-6-yl)methanimine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Nonpeptidic Tetrafluorophenoxymethyl Ketone Cruzain Inhibitors as Promising New Leads for Chagas Disease Chemotherapy

  摘要：

  A century after discovering that file Trypanosoma cruzi parasite is the etiological agent of Chagas disease, treatment is still plagued by limited efficacy, toxicity, and the emergence of drug, resistance. The development of inhibitors of the major T. cruzi cysteine protease, cruzain, has been demonstrated to be a promising drug discovery avenue for this neglected disease. Here we establish that a nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitor Substantially ameliorates symptoms of acute Chagas disease in a mouse model With no apparent toxicity. A high-resolution Crystal Structure confirmed the mode of inhibition and revealed key binding interactions of this novel inhibitor class. Subsequent structure-guided optimization then resulted in inhibitor analogues With improvements in potency despite minimal or no additions in molecular weight. Evaluation Of file analogues in cell Culture showed enhanced activity. These results suggest that nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors have the Potential to fulfill file Urgent need for improved Chagas disease chemotherapy.

  DOI：

  10.1021/jm901633v
• 作为产物：
  描述：

  (3S)-3,4-dimethylpent-1-yn-3-amine 、 喹啉-6-甲醛 以 甲苯 为溶剂， 生成 (S)-N-(3,4-dimethylpent-1-yn-3-yl)-1-(quinolin-6-yl)methanimine
  参考文献：
  名称：

  Nonpeptidic Tetrafluorophenoxymethyl Ketone Cruzain Inhibitors as Promising New Leads for Chagas Disease Chemotherapy

  摘要：

  A century after discovering that file Trypanosoma cruzi parasite is the etiological agent of Chagas disease, treatment is still plagued by limited efficacy, toxicity, and the emergence of drug, resistance. The development of inhibitors of the major T. cruzi cysteine protease, cruzain, has been demonstrated to be a promising drug discovery avenue for this neglected disease. Here we establish that a nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitor Substantially ameliorates symptoms of acute Chagas disease in a mouse model With no apparent toxicity. A high-resolution Crystal Structure confirmed the mode of inhibition and revealed key binding interactions of this novel inhibitor class. Subsequent structure-guided optimization then resulted in inhibitor analogues With improvements in potency despite minimal or no additions in molecular weight. Evaluation Of file analogues in cell Culture showed enhanced activity. These results suggest that nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors have the Potential to fulfill file Urgent need for improved Chagas disease chemotherapy.

  DOI：

  10.1021/jm901633v

文献信息

• [EN] NONPEPTIDIC INHIBITORS OF CRUZAIN<br/>[FR] INHIBITEURS NON PEPTIDIQUES DE LA CRUAZÏNE
  申请人：UNIV CALIFORNIA

  公开号：WO2009075778A3

  公开（公告）日：2009-10-15