[3-[acetyl(phenylmethoxy)amino]propyl]phosphonic acid | 581106-29-8

• 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-[acetyl(phenylmethoxy)amino]propyl]phosphonic acid
• 英文别名: 3-[Acetyl(phenylmethoxy)amino]propylphosphonic acid
• CAS: 581106-29-8
• 化学式: C₁₂H₁₈NO₅P
• 分子量: 287.252
• InChiKey: LSWQRNJXEQARPK-UHFFFAOYSA-N

物化性质

• 熔点：
  145-146 °C
• 沸点：
  481.9±55.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [3-[acetyl(phenylmethoxy)amino]propyl]phosphonic acid 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 [3-[acetyl(phenylmethoxy)amino]propyl]-phosphonic acid monobenzyl ester
  参考文献：
  名称：

  具有改进的体内抗疟活性的 FR900098 的烷氧基羰基氧基乙酯前药

  摘要：

  FR900098 代表具有增强活性的新型抗疟药磷米霉素的衍生物。作用机制是抑制 1-脱氧-D-木酮糖 5-磷酸 (DOXP) 还原异构酶，这是一种非甲羟戊酸类异戊二烯生物合成途径的必需酶。通过将 FR900098 的膦酸酯部分掩蔽为烷氧羰基氧乙酯，获得了在感染了啮齿动物疟原虫 vinckei 的小鼠中具有增加的口服活性的前药。

  DOI：

  10.1002/ardp.200500976
• 作为产物：
  描述：

  benzyloxyiminopropylphosphonic acid diethyl ester 在 盐酸 、 三甲基溴硅烷 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 37.5h， 生成 [3-[acetyl(phenylmethoxy)amino]propyl]phosphonic acid
  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

• [EN] COMPOUNDS FOR INHIBITING 1- DEOXY-D-XYLULOSE- 5 - PHOSPHATE REDUCTOISOMERASE<br/>[FR] COMPOSÉS DESTINÉS À INHIBER LA 1-DÉSOXY-D-XYLULOSE-5-PHOSPHATE RÉDUCTOISOMÉRASE
  申请人：UNIV GEORGE WASHINGTON

  公开号：WO2013006444A1

  公开（公告）日：2013-01-10

  [0082] In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or 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 l-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。本发明涉及具有通式（I）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环芳基团；n为0、1、2、3或4，优选为2、3或4。这些化合物抑制l-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。
• 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。
• Acyloxyalkyl ester prodrugs of FR900098 with improved in vivo anti-malarial activity
  作者：Regina Ortmann、Jochen Wiesner、Armin Reichenberg、Dajana Henschker、Ewald Beck、Hassan Jomaa、Martin Schlitzer

  DOI：10.1016/s0960-894x(03)00354-8

  日期：2003.7

  FR900098 represents an improved derivative of the new antimalarial drug fosmidomycin and acts through inhibition of the 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield acyloxyalkyl

  FR900098代表新的抗疟药fosmidomycin的改良衍生物，并通过抑制1-脱氧-D-木酮糖5-磷酸（DOXP）还原异构酶起作用，该酶是类戊二烯类生物合成的甲羟戊酸独立途径的必需酶。通过化学修饰膦酸酯部分以产生酰氧基烷基酯，可获得口服后活性增强的前药。最成功的化合物在感染了啮齿动物疟疾寄生虫温氏疟原虫的小鼠中显示出2倍的活性增加。
• Double Ester Prodrugs of FR900098 Display EnhancedIn-Vitro Antimalarial Activity
  作者：Jochen Wiesner、Regina Ortmann、Hassan Jomaa、Martin Schlitzer

  DOI：10.1002/ardp.200700069

  日期：2007.12

  Fosmidomycin and FR900098 are inhibitors of the 1‐deoxy‐D‐xylulose 5‐phosphate reductoisomerase (DXR; IspC), a key enzyme of the mevalonate‐independent isoprenoid biosynthesis pathway. We have determined the in‐vitro antimalarial activity of two double ester prodrugs 2, 3 in direct comparison with the unmodified FR900098 1 against intraerythrocytic forms of Plasmodium falciparum. Temporarily masking

  Fosmidomycin 和 FR900098 是 1-脱氧-D-木酮糖 5-磷酸还原异构酶 (DXR; IspC) 的抑制剂，这是一种不依赖甲羟戊酸的类异戊二烯生物合成途径的关键酶。我们已经与未修饰的 FR900098 1 直接比较，确定了两种双酯前药 2、3 对红细胞内形式的恶性疟原虫的体外抗疟活性。暂时掩盖 DXR 抑制剂 FR900098 1 膦酸酯部分的极性特性不仅增强了其口服生物利用度，而且增强了该系列对寄生虫的内在活性。
• COMPOUNDS FOR INHIBITING 1-DEOXY-D-XYLULOSE-5-PHOSPHATE REDUCTOISOMERASE
  申请人：Boshoff Helena I.

  公开号：US20140378418A1

  公开（公告）日：2014-12-25

  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).

  特别地，该化合物对于抑制结核分枝杆菌（Mtb）中的Dxr具有有效性。本发明涉及具有通式（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环芳香基团；n为0、1、2、3或4，优选为2、3或4。该化合物抑制1-脱氧-D-木糖-5-磷酸还原异构酶（Dxr），特别是在结核分枝杆菌（Mtb）中的Dxr。