diethyl 3-oxo-1-(2-(thiophen-2-yl)phenyl)propylphosphonate | 1313733-81-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl 3-oxo-1-(2-(thiophen-2-yl)phenyl)propylphosphonate
• 英文别名: 3-Diethoxyphosphoryl-3-(2-thiophen-2-ylphenyl)propanal
• CAS: 1313733-81-1
• 化学式: C₁₇H₂₁O₄PS
• 分子量: 352.391
• InChiKey: QHKRASHUAUMYTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl 3-oxo-1-(2-(thiophen-2-yl)phenyl)propylphosphonate 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 吡啶 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.5h， 生成 diethyl 3-(N-hydroxyacetamido)-1-(2-(thiophen-2-yl)phenyl)propylphosphonate
  参考文献：
  名称：

  Design, Synthesis, and X-ray Crystallographic Studies of α-Aryl Substituted Fosmidomycin Analogues as Inhibitors ofMycobacterium tuberculosis1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase

  摘要：

  The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC50 = 0.15 mu M on MtDXR but still lacked activity in a mycobacterial growth assay (MIC > 32 mu g/mL). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite.

  DOI：

  10.1021/jm2000085
• 作为产物：
  描述：

  2-溴苯基硼酸 在 新铜试剂 、 palladium diacetate 、 potassium carbonate 、 对苯醌 、 tri tert-butylphosphoniumtetrafluoroborate 、 苯酚 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 26.75h， 生成 diethyl 3-oxo-1-(2-(thiophen-2-yl)phenyl)propylphosphonate
  参考文献：
  名称：

  Design, Synthesis, and X-ray Crystallographic Studies of α-Aryl Substituted Fosmidomycin Analogues as Inhibitors ofMycobacterium tuberculosis1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase

  摘要：

  The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC50 = 0.15 mu M on MtDXR but still lacked activity in a mycobacterial growth assay (MIC > 32 mu g/mL). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite.

  DOI：

  10.1021/jm2000085