ethyl 2-((benzylamino)methyl)-2-((tert-butoxycarbonyl)amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate | 1428265-92-2

• 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: ethyl 2-((benzylamino)methyl)-2-((tert-butoxycarbonyl)amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate
• CAS: 1428265-92-2
• 化学式: C₂₇H₄₅BN₂O₆
• 分子量: 504.475
• InChiKey: HIGKYXDLXURWPS-UHFFFAOYSA-N

物化性质

• 沸点：
  581.5±50.0 °C(predicted)
• 密度：
  1.07±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  36.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  95.12
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-((benzylamino)methyl)-2-((tert-butoxycarbonyl)amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate 在 盐酸 作用下， 反应 16.0h， 生成 2-amino-2-((benzylamino)methyl)-6-boronohexanoic acid
  参考文献：
  名称：

  2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors

  摘要：

  Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase land arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.024
• 作为产物：
  描述：

  二乙基(Boc-氨基)乙酯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 草酰氯 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 1,2-双(二苯基膦)乙烷 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.5h， 生成 ethyl 2-((benzylamino)methyl)-2-((tert-butoxycarbonyl)amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate
  参考文献：
  名称：

  2-Substituted-2-amino-6-boronohexanoic acids as arginase inhibitors

  摘要：

  Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase land arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme isoforms. This potency improvement can be rationalized by X-ray crystallography, which shows a water-mediated contact between the basic nitrogen and the carboxylic acid side chain of Asp200, which is situated at the mouth of the active site pocket of arginase II (Asp181 in arginase I). We believe that this is the first literature report of compounds with improved arginase inhibitory activity, relative to ABH, and represents a promising starting point for further optimization of in vitro potency and the identification of better tool molecules for in vivo investigations of the potential pathophysiological roles of arginases. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.024