hexadecyl-2',3'-isopropylidenuridin-5'-ylvinylphosphonate | 1344121-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: hexadecyl-2',3'-isopropylidenuridin-5'-ylvinylphosphonate
• 英文别名: hexadecyl 2',3'-isopropylideneuridin-5'-yl vinylphosphonate；1-[(3aR,4R,6R,6aR)-6-[[ethenyl(hexadecoxy)phosphoryl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione
• CAS: 1344121-66-9
• 化学式: C₃₀H₅₁N₂O₈P
• 分子量: 598.717
• InChiKey: LRLFNPXJBMOFNM-NPFAQEMZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  41
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  hexadecyl-2',3'-isopropylidenuridin-5'-ylvinylphosphonate 在 盐酸 作用下， 以 甲醇 、 正丁醇 为溶剂， 反应 4.0h， 生成 hexadecyl uridin-5'-yl 2-([3R,5S]-3-hydroxy-5-(hydroxymethyl)pyrrolidin-1-N-yl)ethylphosphonate
  参考文献：
  名称：

  Lipophosphonoxins: New Modular Molecular Structures with Significant Antibacterial Properties

  摘要：

  Novel compounds termed lipophosphonoxins were prepared using a simple and efficient synthetic approach. The general structure of lipophosphonoxins consists of four modules: (i) a nucleoside module, (ii) an iminosugar module, (iii) a hydrophobic module (lipophilic alkyl chain), and (iv) a phosphonate linker module that holds together modules i-iii. Lipophosphonoxins displayed significant antibacterial properties against a panel of Gram-positive species, including multiresistant strains. The minimum inhibitory concentration (MIC) values of the best inhibitors were in the 1-12 mu g/mL range, while their cytotoxic concentrations against human cell lines were significantly above this range. The modular nature of this artificial scaffold offers a large number of possibilities for further modifications/exploitation of these compounds.

  DOI：

  10.1021/jm2009343
• 作为产物：
  描述：

  1-十六烷醇 、 在 2,4,6-三异丙基苯磺酰氯 作用下， 以 二氯甲烷 为溶剂， 以38%的产率得到hexadecyl-2',3'-isopropylidenuridin-5'-ylvinylphosphonate
  参考文献：
  名称：

  Lipophosphonoxins: New Modular Molecular Structures with Significant Antibacterial Properties

  摘要：

  Novel compounds termed lipophosphonoxins were prepared using a simple and efficient synthetic approach. The general structure of lipophosphonoxins consists of four modules: (i) a nucleoside module, (ii) an iminosugar module, (iii) a hydrophobic module (lipophilic alkyl chain), and (iv) a phosphonate linker module that holds together modules i-iii. Lipophosphonoxins displayed significant antibacterial properties against a panel of Gram-positive species, including multiresistant strains. The minimum inhibitory concentration (MIC) values of the best inhibitors were in the 1-12 mu g/mL range, while their cytotoxic concentrations against human cell lines were significantly above this range. The modular nature of this artificial scaffold offers a large number of possibilities for further modifications/exploitation of these compounds.

  DOI：

  10.1021/jm2009343

文献信息

• [EN] LIPOPHOSPHONOXINS OF SECOND GENERATION, AND THEIR USE<br/>[FR] LIPOPHOSPHONOXINES DE SECONDE GÉNÉRATION ET LEUR UTILISATION
  申请人：USTAV ORGANICKE CHEMIE A BIOCHEMIE AV CR V V I

  公开号：WO2017186200A1

  公开（公告）日：2017-11-02

  Lipophosphonoxins of general Formula I are described here, wherein R1 is C8-C22, preferably C10-C18 and more preferably C12-C16 alkyl, or hexadecyloxypropyl, tetradecyloxypropyl, tetradecyloxyethyl or hexadecyloxyethyl, R2 is uracil, thymine, or cytosine, R3 is selected from a group which contains compounds of general formulas II and III, wherein R4 is H, CH2OH or CH2NH2, R5 is H, OH or NH2, R6 is H, OH or NH2, R7 is H, CH2OH or CH2NH2, wherein at least one of the groups R5 and R6 must be NH2 or one of the groups R4 and R7 must be CH2NH2. R8 is H, CH2OH or CH2NH2, R9 is H, OH or NH2, R10 is H, OH or NH2, R11 is H, OH or NH2, R12 is H, CH2OH or CH2NH2, wherein at least one of the groups R9, R10 and R11 must be NH2 or one of the groups R8 a R12 must be CH2NH2. R13 is NH2 or NH-CH(NH2)NH, R14 is NH2 or NH-CH(NH2)NH, R15 is NH2 or NH-CH(NH2)NH, R16 is NH2 or NH-CH(NH2)NH. Further, diastereomers and mixtures of diastereomers of compounds of general formula I and the corresponding pharmaceutically acceptable salts and/or hydrates are described. The compounds of general formula I are useful as antibacterial agents or active ingredients in disinfectants, and/or of selective in vitro culture media.

  本文描述了一般式I的脂肪磷酸诺酮，其中R1为C8-C22，优选为C10-C18，更优选为C12-C16烷基，或十六烷氧基丙基，十四烷氧基丙基，十四烷氧基乙基或十六烷氧基乙基，R2为尿嘧啶，胸腺嘧啶或胞嘧啶，R3从一组化合物中选择，该组化合物包含一般式II和III，其中R4为H，CH2OH或CH2NH2，R5为H，OH或NH2，R6为H，OH或NH2，R7为H，CH2OH或CH2NH2，其中R5和R6中至少有一个必须为NH2，或者R4和R7中的一个必须为CH2NH2。R8为H，CH2OH或CH2NH2，R9为H，OH或NH2，R10为H，OH或NH2，R11为H，OH或NH2，R12为H，CH2OH或CH2NH2，其中R9、R10和R11中至少有一个必须为NH2，或者R8和R12中的一个必须为CH2NH2。R13为NH2或NH-CH（NH2）NH，R14为NH2或NH-CH（NH2）NH，R15为NH2或NH-CH（NH2）NH，R16为NH2或NH-CH（NH2）NH。此外，还描述了一般式I的对映异构体和对应的药学上可接受的盐和/或水合物的混合物。一般式I的化合物可用作抗菌剂或消毒剂的活性成分和/或体外选择性培养基。
• Lipophosphonoxins, method of their preparation and use
  申请人：Ustav organicke chemie a biochemie AV CR, v.v.i.

  公开号：EP2527351B1

  公开（公告）日：2013-12-11
• Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents
  作者：Gabriela Seydlová、Radek Pohl、Eva Zborníková、Marcel Ehn、Ondřej Šimák、Natalya Panova、Milan Kolář、Kateřina Bogdanová、Renata Večeřová、Radovan Fišer、Hana Šanderová、Dragana Vítovská、Petra Sudzinová、Jiří Pospíšil、Oldřich Benada、Tomáš Křížek、David Sedlák、Petr Bartůněk、Libor Krásný、Dominik Rejman

  DOI：10.1021/acs.jmedchem.7b00355

  日期：2017.7.27

  The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and-negative bacteria, including pathogens and multiresistant strains. We describe their mechanism of action plasmatic membrane pore-forming activity selective for bacteria. Importantly, LPPO II neither damage nor cross the eukaryotic plasmatic membrane at their bactericidal concentrations. Further, we LPPO II have low propensity for resistance development, likely due to their rapid membrane-targeting mode of action. Finally, we reveal that LPPO II are not toxic to either eukaryotic cells or model animals when administered orally or topically. Collectively, these results suggest that LPPO II are highly promising compounds for development into pharmaceuticals.
• Lipophosphonoxins: New Modular Molecular Structures with Significant Antibacterial Properties
  作者：Dominik Rejman、Alžbeta Rabatinová、António R. Pombinho、Soňa Kovačková、Radek Pohl、Eva Zbornı́ková、Milan Kolář、Kateřina Bogdanová、Otakar Nyč、Hana Šanderová、Tomáš Látal、Petr Bartůněk、Libor Krásný

  DOI：10.1021/jm2009343

  日期：2011.11.24

  Novel compounds termed lipophosphonoxins were prepared using a simple and efficient synthetic approach. The general structure of lipophosphonoxins consists of four modules: (i) a nucleoside module, (ii) an iminosugar module, (iii) a hydrophobic module (lipophilic alkyl chain), and (iv) a phosphonate linker module that holds together modules i-iii. Lipophosphonoxins displayed significant antibacterial properties against a panel of Gram-positive species, including multiresistant strains. The minimum inhibitory concentration (MIC) values of the best inhibitors were in the 1-12 mu g/mL range, while their cytotoxic concentrations against human cell lines were significantly above this range. The modular nature of this artificial scaffold offers a large number of possibilities for further modifications/exploitation of these compounds.