N-hydroxy-(5-phenylpyridine-2-yl)acetamide | 1311150-70-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-hydroxy-(5-phenylpyridine-2-yl)acetamide
• 英文别名: N-hydroxy-2-(5-phenylpyridin-2-yl)acetamide
• CAS: 1311150-70-5
• 化学式: C₁₃H₁₂N₂O₂
• 分子量: 228.25
• InChiKey: AEGAJIAIIQYEDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(5-溴吡啶-2-基)乙酸甲酯 在 甲醇 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 3.0h， 生成 N-hydroxy-(5-phenylpyridine-2-yl)acetamide
  参考文献：
  名称：

  Inhibition of 1-Deoxy-d-Xylulose-5-Phosphate Reductoisomerase by Lipophilic Phosphonates: SAR, QSAR, and Crystallographic Studies

  摘要：

  1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K-i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a, MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.

  DOI：

  10.1021/jm200363d

文献信息

• [EN] NOVEL DXR INHIBITORS FOR ANTIMICROBIAL THERAPY<br/>[FR] NOUVEAUX INHIBITEURS DE DXR POUR THÉRAPIE ANTIMICROBIENNE
  申请人：BAYLOR COLLEGE MEDICINE

  公开号：WO2011046920A1

  公开（公告）日：2011-04-21

  The present invention generally concerns particular methods and compositions for antimicrobial therapy. In particuarl embodiments, the compositions target DXR. In specific embodiments, the compositions are electron-deficient heterocyclic rings.

  本发明一般涉及特定的抗微生物治疗方法和组合物。在特定实施例中，这些组合物以DXR为靶点。在具体实施例中，这些组合物是电子亏缺的杂环环。
• NOVEL DXR INHIBITORS FOR ANTIMICROBIAL THERAPY
  申请人：Song Yongcheng

  公开号：US20130065857A1

  公开（公告）日：2013-03-14

  The present invention generally concerns particular methods and compositions for antimicrobial therapy. In particular embodiments, the compositions target DXR. In specific embodiments, the compositions are electron-deficient heterocyclic rings.

  本发明通常涉及特定的抗微生物治疗方法和组合物。在特定实施例中，该组合物针对DXR。在具体实施例中，该组合物是电子不足的杂环环。
• Inhibition of 1-Deoxy-<scp>d</scp>-Xylulose-5-Phosphate Reductoisomerase by Lipophilic Phosphonates: SAR, QSAR, and Crystallographic Studies
  作者：Lisheng Deng、Jiasheng Diao、Pinhong Chen、Venugopal Pujari、Yuan Yao、Gang Cheng、Dean C. Crick、B. V. Venkataram Prasad、Yongcheng Song

  DOI：10.1021/jm200363d

  日期：2011.7.14

  1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K-i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a, MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.