5-Fluoro-N-{[(quinolin-3-yl)methoxy]carbonyl}-L-tryptophan | 918440-81-0

• 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: 5-Fluoro-N-{[(quinolin-3-yl)methoxy]carbonyl}-L-tryptophan
• 英文别名: (2S)-3-(5-fluoro-1H-indol-3-yl)-2-(quinolin-3-ylmethoxycarbonylamino)propanoic acid
• CAS: 918440-81-0
• 化学式: C₂₂H₁₈FN₃O₄
• 分子量: 407.401
• InChiKey: IRHYNOVXYXYKMN-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-Fluoro-N-{[(quinolin-3-yl)methoxy]carbonyl}-L-tryptophan 、 (3-bromo-4,5-dihydroisoxazol-5-yl)methanamine 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-二甲基甲酰胺 为溶剂， 以75%的产率得到(S)-quinolin-3-ylmethyl 1-((3-bromo-4,5-dihydroisoxazol-5-yl)methylamino)-3-(5-fluoro-1H-indol-3-yl)-1-oxopropan-2-ylcarbamate
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of the Selective Inhibition of Transglutaminase 2 by Dihydroisoxazoles

  摘要：

  Human transglutaminase 2 (TG2) is believed to play an important role in the pathogenesis of various human disorders including celiac sprue, certain neurological diseases, and some types of cancer. Selective inhibition of TG2 should therefore enable further investigation of its role in physiology and disease and may lead to effective clinical treatment. Recently we showed that certain 3-halo-4-,5-dihydroisoxazole containing compounds are selective inhibitors of human TG2 with promising pharmacological activities. Here, we present definitive evidence that this class of compounds targets the active site of human TG2. Structure-activity relationship studies have provided insights into the structural prerequisites for selectivity and have led to the discovery of an inhibitor with about 50-fold higher activity than a prototypical dihydroisoxazole inhibitor with good in vivo activity. A method for preparing enantiomerically enriched analogues was also developed. Our studies show that the 5-(S)-dihydroisoxazole is a markedly better inhibitor of human TG2 than its 5-(R) stereoisomer.

  DOI：

  10.1021/jm060839a
• 作为产物：
  描述：

  喹啉-3-基甲醇 在 N-甲基吗啉 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 5-Fluoro-N-{[(quinolin-3-yl)methoxy]carbonyl}-L-tryptophan
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of the Selective Inhibition of Transglutaminase 2 by Dihydroisoxazoles

  摘要：

  Human transglutaminase 2 (TG2) is believed to play an important role in the pathogenesis of various human disorders including celiac sprue, certain neurological diseases, and some types of cancer. Selective inhibition of TG2 should therefore enable further investigation of its role in physiology and disease and may lead to effective clinical treatment. Recently we showed that certain 3-halo-4-,5-dihydroisoxazole containing compounds are selective inhibitors of human TG2 with promising pharmacological activities. Here, we present definitive evidence that this class of compounds targets the active site of human TG2. Structure-activity relationship studies have provided insights into the structural prerequisites for selectivity and have led to the discovery of an inhibitor with about 50-fold higher activity than a prototypical dihydroisoxazole inhibitor with good in vivo activity. A method for preparing enantiomerically enriched analogues was also developed. Our studies show that the 5-(S)-dihydroisoxazole is a markedly better inhibitor of human TG2 than its 5-(R) stereoisomer.

  DOI：

  10.1021/jm060839a