N-(3-dihexoxyphosphorylpropyl)-N-hydroxy-acetamide | 1350649-65-8

• 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: N-(3-dihexoxyphosphorylpropyl)-N-hydroxy-acetamide
• 英文别名: N-(3-dihexoxyphosphorylpropyl)-N-hydroxyacetamide
• CAS: 1350649-65-8
• 化学式: C₁₇H₃₆NO₅P
• 分子量: 365.45
• InChiKey: ZOXKUFPGKXEZOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  diethyl (3-(N-(benzyloxy)acetamido)propyl)phosphonate 在 三甲基溴硅烷 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 N-(3-dihexoxyphosphorylpropyl)-N-hydroxy-acetamide
  参考文献：
  名称：

  Antibacterial and antitubercular activity of fosmidomycin, FR900098, and their lipophilic analogs

  摘要：

  The nonmevalonate pathway (NMP) of isoprene biosynthesis is an exciting new route toward novel antibiotic development. Inhibitors against several enzymes in this pathway are currently under examination. A significant liability of many of these agents is poor cell penetration. To overcome and improve our understanding of this problem, we have synthesized a series of lipophilic, prodrug analogs of fosmidomycin and FR900098, inhibitors of the NMP enzyme Dxr. Several of these compounds show improved antibacterial activity against a panel of organisms relative to the parent compound, including activity against Mycobacterium tuberculosis (Mtb). Our results show that this strategy can be an effective way for improving whole cell activity of NMP inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.123

文献信息

• Compounds for inhibiting 1-deoxy-D-xylulose-5-phosphate reductoisomerase
  申请人：Boshoff Helena I.

  公开号：US09593136B2

  公开（公告）日：2017-03-14

  In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or (II) where X is an acidic group, such as carboxylate, phosphonate, sulfate, and tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, preferably 2, 3, or 4. The compounds inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), particularly Dxr in Mycobacterium tuberculosis (Mtb).

  特别是，该化合物能有效抑制结核分枝杆菌（Mtb）中的Dxr。本发明涉及具有一般式（I）或（II）的化合物 其中X是酸性基团，如羧酸盐、膦酸盐、硫酸盐和四唑基；Ar是取代或未取代的芳香或杂芳基团；n为0、1、2、3或4，优选为2、3或4。这些化合物抑制1-脱氧-D-木糖-5-磷酸还原异构酶（Dxr），特别是结核分枝杆菌（Mtb）中的Dxr。
• Antibacterial and antitubercular activity of fosmidomycin, FR900098, and their lipophilic analogs
  作者：Eugene Uh、Emily R. Jackson、Géraldine San Jose、Marcus Maddox、Robin E. Lee、Richard E. Lee、Helena I. Boshoff、Cynthia S. Dowd

  DOI：10.1016/j.bmcl.2011.09.123

  日期：2011.12

  The nonmevalonate pathway (NMP) of isoprene biosynthesis is an exciting new route toward novel antibiotic development. Inhibitors against several enzymes in this pathway are currently under examination. A significant liability of many of these agents is poor cell penetration. To overcome and improve our understanding of this problem, we have synthesized a series of lipophilic, prodrug analogs of fosmidomycin and FR900098, inhibitors of the NMP enzyme Dxr. Several of these compounds show improved antibacterial activity against a panel of organisms relative to the parent compound, including activity against Mycobacterium tuberculosis (Mtb). Our results show that this strategy can be an effective way for improving whole cell activity of NMP inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.