(1R)-2-[4-(3-carboxyphenyl)[1,2,3]triazol-1-yl]-1-(2-thienylacetylamino)ethaneboronic acid | 1429666-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (1R)-2-[4-(3-carboxyphenyl)[1,2,3]triazol-1-yl]-1-(2-thienylacetylamino)ethaneboronic acid
• 英文别名: boronic acid transition state inhibitor S03043；3-[1-[(2R)-2-borono-2-[(2-thiophen-2-ylacetyl)amino]ethyl]triazol-4-yl]benzoic acid
• CAS: 1429666-58-9
• 化学式: C₁₇H₁₇BN₄O₅S
• 分子量: 400.223
• InChiKey: WHXOLIBPKXZPTN-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.44
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  8

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 甲醇 、 正己烷 、 水 、 叔丁醇 为溶剂， 反应 2.0h， 生成 (1R)-2-[4-(3-carboxyphenyl)[1,2,3]triazol-1-yl]-1-(2-thienylacetylamino)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

文献信息

• Inhibition of <i>Acinetobacter</i>-Derived Cephalosporinase: Exploring the Carboxylate Recognition Site Using Novel β-Lactamase Inhibitors
  作者：Emilia Caselli、Chiara Romagnoli、Rachel A. Powers、Magdalena A. Taracila、Alexandra A. Bouza、Hollister C. Swanson、Kali A. Smolen、Francesco Fini、Bradley J. Wallar、Robert A. Bonomo、Fabio Prati

  DOI：10.1021/acsinfecdis.7b00153

  日期：2018.3.9

  Boronic acids are attracting a lot of attention as β-lactamase inhibitors, and in particular, compound S02030 (Ki = 44 nM) proved to be a good lead compound against ADC-7 (Acinetobacter-derived cephalosporinase), one of the most significant resistance determinants in A. baumannii. The atomic structure of the ADC-7/S02030 complex highlighted the importance of critical structural determinants for recognition

  硼酸作为β-内酰胺酶抑制剂引起了广泛的关注，特别是化合物S02030（K i = 44 nM）被证明是对抗ADC-7（不动杆菌衍生的头孢菌素酶）的良好先导化合物，ADC-7是最重要的化合物之一。鲍曼不动杆菌中的抗性决定因素。ADC-7 / S02030配合物的原子结构突显了关键结构决定因素对于识别硼酸的重要性。在本文中，为了阐明在识别R2-羧酸酯（模拟在β-内酰胺中发现的C 3 / C 4）中的作用，我们设计，合成并表征了S02030的六种衍生物（3a）。在这六种化合物中，最好的抑制剂被证明是带有明显负电荷的化合物（化合物3a – c，3h和3j，K i = 44–115 nM），这与衍生物的负电荷相反。诸如酰胺衍生物3d（K i＝ 224nM）和羟酰胺衍生物3e（K i＝ 155nM）被省略。为了开发抑制剂在活性位点结合的结构特征，ADC-7与化合物3c，SM23和EC04的复合物的X射