3-pyrimidin-2-yl-N-[3-(1H-tetrazol-5-yl)phenyl]benzamide | 1357581-99-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-pyrimidin-2-yl-N-[3-(1H-tetrazol-5-yl)phenyl]benzamide
• 英文别名: 3-(Pyrimidin-2-Yl)-N-[3-(1h-Tetrazol-5-Yl)phenyl]benzamide；3-pyrimidin-2-yl-N-[3-(2H-tetrazol-5-yl)phenyl]benzamide
• CAS: 1357581-99-7
• 化学式: C₁₈H₁₃N₇O
• 分子量: 343.348
• InChiKey: WMPLYYWUNLVUAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(3-氨基苯基)四唑 、 3-嘧啶-2-基-苯甲醛 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以11%的产率得到3-pyrimidin-2-yl-N-[3-(1H-tetrazol-5-yl)phenyl]benzamide
  参考文献：
  名称：

  Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A β-Lactamase

  摘要：

  The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K-i = 21 mu M) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K-i value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli. The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design.

  DOI：

  10.1021/jm2014138

文献信息

• Compositions, methods of use, and methods of treatment
  申请人：University of South Florida

  公开号：US10604493B2

  公开（公告）日：2020-03-31

  Embodiments of the present disclosure, in one aspect, relate to a beta-lactamase inhibitor, pharmaceutical compositions including a beta-lactamase inhibitor, methods of treatment of a condition (e.g., infection) or disease, methods of treatment using compositions or pharmaceutical compositions, and the like.

  本公开的实施方案在一个方面涉及β-内酰胺酶抑制剂、包括β-内酰胺酶抑制剂的药物组合物、治疗病症（如感染）或疾病的方法、使用组合物或药物组合物的治疗方法等。
• Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A β-Lactamase
  作者：Derek A. Nichols、Priyadarshini Jaishankar、Wayne Larson、Emmanuel Smith、Guoqing Liu、Racha Beyrouthy、Richard Bonnet、Adam R. Renslo、Yu Chen

  DOI：10.1021/jm2014138

  日期：2012.3.8

  The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K-i = 21 mu M) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K-i value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli. The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design.