2-(Diethoxyphosphorylmethyl)pyrazine | 581800-66-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: 2-(Diethoxyphosphorylmethyl)pyrazine
• CAS: 581800-66-0
• 化学式: C₉H₁₅N₂O₃P
• 分子量: 230.203
• InChiKey: XZSJEPIEWNGFSI-UHFFFAOYSA-N

物化性质

• 沸点：
  342.1±32.0 °C(Predicted)
• 密度：
  1.179±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(Diethoxyphosphorylmethyl)pyrazine 在 三甲基溴硅烷 、 甲醇 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 以1.46 g的产率得到pyrazin-2-ylmethylphosphonic acid disodium salt
  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
• 作为产物：
  描述：

  2-甲基吡嗪 在 N-氯代丁二酰亚胺 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 生成 2-(Diethoxyphosphorylmethyl)pyrazine
  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

• Alpha-substituted heteroarylalkyl phosphonate derivatives
  申请人：Phan Trung Hieu

  公开号：US20050124581A1

  公开（公告）日：2005-06-09

  The present invention relates to novel α-substituted heteroarylalkylphosphonate derivatives and their uses for lowering plasma levels of apo (a), Lp(a), apo B, apo B associated lipoproteins (low density lipoproteins and very low density lipoproteins) and for lowering plasma levels of total cholesterol.

  本发明涉及新型的α-取代杂环烷基膦酸酯衍生物及其用于降低血浆apo（a）、Lp（a）、apo B、apo B相关脂蛋白（低密度脂蛋白和超低密度脂蛋白）和降低总胆固醇血浆水平的用途。
• ALPHA-SUBSTITUTED HETEROARYLALKYL PHOSPHONATE DERIVATTIVES
  申请人：Ilex Products, Inc.

  公开号：EP1482953A1

  公开（公告）日：2004-12-08
• EP1482953A4
  申请人：——

  公开号：EP1482953A4

  公开（公告）日：2006-12-13
• [EN] ALPHA-SUBSTITUTED HETEROARYLALKYL PHOSPHONATE DERIVATTIVES<br/>[FR] DERIVES ALPHA-SUBSTITUES D'HETEROARYLALKYL PHOSPHONATE
  申请人：ILEX PRODUCTS INC

  公开号：WO2003068240A1

  公开（公告）日：2003-08-21

  The present invention relates to novel α-substituted heteroarylalkylphosphonate derivatives and their uses for lowering plasma levels of apo (a), Lp(a), apo B, apo B associated lipoproteins (low density lipoproteins and very low density lipoproteins) and for lowering plasma levels of total cholesterol.