2-amino-6-borono-2-(difluoromethyl)hexanoic acid | 1315342-51-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-amino-6-borono-2-(difluoromethyl)hexanoic acid
• 英文别名: 2-Azaniumyl-6-borono-2-(difluoromethyl)hexanoate
• CAS: 1315342-51-8
• 化学式: C₇H₁₄BF₂NO₄
• 分子量: 225.0
• InChiKey: QIYCLWKKKPVZJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.32
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 2-N-(diphenylmethyleneamino)-2-difluoromethyl-6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)hexanoate 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以92%的产率得到2-amino-6-borono-2-(difluoromethyl)hexanoic acid
  参考文献：
  名称：

  Binding of α,α-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

  摘要：

  Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of α,α-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional α-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.

  DOI：

  10.1021/jm200443b

文献信息

• Binding of α,α-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design
  作者：Monica Ilies、Luigi Di Costanzo、Daniel P. Dowling、Katherine J. Thorn、David W. Christianson

  DOI：10.1021/jm200443b

  日期：2011.8.11

  Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of α,α-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional α-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.