2-(4-phenyl-[1,2,3]triazol-1-yl)-1S-(2-thiophen-2-yl-acetylamino)ethaneboronic acid | 1429666-57-8

• 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-phenyl-[1,2,3]triazol-1-yl)-1S-(2-thiophen-2-yl-acetylamino)ethaneboronic acid
• 英文别名: (1R)-2-(4-phenyl[1,2,3]triazol-1-yl)-1-[(2-thienylacetyl)amino]ethaneboronic acid；[(1R)-2-(4-phenyltriazol-1-yl)-1-[(2-thiophen-2-ylacetyl)amino]ethyl]boronic acid
• CAS: 1429666-57-8
• 化学式: C₁₆H₁₇BN₄O₃S
• 分子量: 356.213
• InChiKey: RMCDOIPZMLAQDA-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.75
• 重原子数：
  25
• 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：
  129
• 氢给体数：
  3
• 氢受体数：
  6

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-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

文献信息

• [EN] BORONIC ACID INHIBITORS OF BETA-LACTAMASES<br/>[FR] INHIBITEURS DE TYPE ACIDE BORONIQUE DE BÊTA-LACTAMASES
  申请人：THERABOR PHARMACEUTICALS

  公开号：WO2013053372A1

  公开（公告）日：2013-04-18

  The invention relates to novel boronic acid compounds, a method for the preparation of such compounds, intermediate compounds for the preparation of such compounds, intermediate compounds for the use in a method for preparation of such compounds, a pharmaceutical composition, the use of one or more compounds discussed above or of a pharmaceutical composition in the manufacture of a medicament for the treatment of a bacterial infection, and a screening method.

  这项发明涉及新型硼酸化合物，一种制备这种化合物的方法，用于制备这种化合物的中间化合物，用于制备这种化合物的方法中间化合物，一种药物组合物，上述一种或多种化合物或药物组合物在制造治疗细菌感染药物的药物制剂中的使用，以及一种筛选方法。
• Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors
  作者：Emilia Caselli、Chiara Romagnoli、Roza Vahabi、Magdalena A. Taracila、Robert A. Bonomo、Fabio Prati

  DOI：10.1021/acs.jmedchem.5b00341

  日期：2015.7.23

  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.