2-[4-(3-amino-phenyl)-[1,2,3]triazol-1-yl]-1S-(2-thiophen-2-yl-acetylamino)ethaneboronic acid | 1429666-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[4-(3-amino-phenyl)-[1,2,3]triazol-1-yl]-1S-(2-thiophen-2-yl-acetylamino)ethaneboronic acid
• 英文别名: (1R)-2-[4-(3-aminophenyl)[1,2,3]triazol-1-yl]-1-[(2-thienylacetyl)amino]ethaneboronic acid；[(1R)-2-[4-(3-aminophenyl)triazol-1-yl]-1-[(2-thiophen-2-ylacetyl)amino]ethyl]boronic acid
• CAS: 1429666-59-0
• 化学式: C₁₆H₁₈BN₅O₃S
• 分子量: 371.228
• InChiKey: XHDDNBKGPAEKIK-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.33
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (+)-pinanediol (1R)-2-azido-1-[(2-thienylacetyl)amino]ethaneboronate 在 盐酸 、 copper(II) sulfate 、 sodium ascorbate 、 苯硼酸 作用下， 以 正己烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 2.0h， 生成 2-[4-(3-amino-phenyl)-[1,2,3]triazol-1-yl]-1S-(2-thiophen-2-yl-acetylamino)ethaneboronic acid
  参考文献：
  名称：

  Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors

  摘要：

  Boronic acid transition-state inhibitors (BAT-SIs) represent one of the most promising classes of beta-lactamase inhibitors. Here we describe a new class of BATSIs, namely, 1-amido-2-triazolylethaneboronic acids, which were synthesized by combining the asymmetric homologation of boronates with copper-catalyzed azide-alkyne cycloaddition for the stereoselective insertion of the amido group and the regioselective formation of the 1,4-disubstituted triazole, respectively. This synthetic pathway, which avoids intermediate purifications, proved to be flexible and efficient, affording in good yields a panel of 14 BATSIs bearing three different R1 amide side chains (acetamido, benzylamido, and 2-thienylacetamido) and Several R substituents on the triazole. This small library was tested against two clinically relevant class C beta-lactamases from Enterobacter spp. and Pseudomonas aeruginosa. The K-i value of the best compound (13a) was as low as 4 nM with significant reduction of bacterial resistance to the combination of cefotaxime/13a.

  DOI：

  10.1021/acs.jmedchem.5b00341