(2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(7-bromo-3-(ethoxycarbonyl)-4-oxoquinolin-1(4H)-yl)tetrahydrofuran-3,4-diyl dibenzoate | 224175-69-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(7-bromo-3-(ethoxycarbonyl)-4-oxoquinolin-1(4H)-yl)tetrahydrofuran-3,4-diyl dibenzoate
• CAS: 224175-69-3
• 化学式: C₃₈H₃₀BrNO₁₀
• 分子量: 740.561
• InChiKey: JUKMNNGPWBVDTN-DWNQJFHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.15
• 重原子数：
  50.0
• 可旋转键数：
  10.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  136.43
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(7-bromo-3-(ethoxycarbonyl)-4-oxoquinolin-1(4H)-yl)tetrahydrofuran-3,4-diyl dibenzoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 7-bromo-1,4-dihydro-4-oxo-1-(β-D-ribofuranosyl)quinoline-3-carboxylic acid
  参考文献：
  名称：

  Molecular design, synthesis and biological evaluation of 1,4-dihydro-4-oxoquinoline ribonucleosides as TcGAPDH inhibitors with trypanocidal activity

  摘要：

  The 1,4-dihydro-4-oxoquinoline ribonucleoside, Neq135, is the first low micromolar trypanosomatidae inhibitor to show good ligand efficiency (0.28 kcal mol(-1) atom(-1)) and good ligand lipophilicity efficiency (0.37 kcal mol(-1) atom(-1)) when acting against Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH). This and other six ribonucleosides were synthesized using our in-house technology, and assayed against the GAPDH NAD(+) site using isothermal titration calorimetry (ITC). Compound Neq135 had acceptable in vitro cytotoxicity, inhibited TcGAPDH with a K-i(app) value of 16 mu M and killed the trypomastigote form of Trypanosoma cruzi Tulahuen strain with a concentration similar to that displayed by the control drug benznidazole. Neq135 is tenfold lower kinetic affinity against hGAPDH and does not kill Balb-c fibroblast nor spleen mouse cells. These results emphasize the possibility of integrating ligand- and target-based designs to uncover potent and selective TcGAPDH inhibitors that expands the opportunity for further medicinal chemistry endeavor towards NAD(+) TcGAPDH site. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.029
• 作为产物：
  描述：

  7-溴-4-羟基喹啉-3-甲酸乙酯 在 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 7.0h， 生成 (2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(7-bromo-3-(ethoxycarbonyl)-4-oxoquinolin-1(4H)-yl)tetrahydrofuran-3,4-diyl dibenzoate
  参考文献：
  名称：

  Molecular design, synthesis and biological evaluation of 1,4-dihydro-4-oxoquinoline ribonucleosides as TcGAPDH inhibitors with trypanocidal activity

  摘要：

  The 1,4-dihydro-4-oxoquinoline ribonucleoside, Neq135, is the first low micromolar trypanosomatidae inhibitor to show good ligand efficiency (0.28 kcal mol(-1) atom(-1)) and good ligand lipophilicity efficiency (0.37 kcal mol(-1) atom(-1)) when acting against Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH). This and other six ribonucleosides were synthesized using our in-house technology, and assayed against the GAPDH NAD(+) site using isothermal titration calorimetry (ITC). Compound Neq135 had acceptable in vitro cytotoxicity, inhibited TcGAPDH with a K-i(app) value of 16 mu M and killed the trypomastigote form of Trypanosoma cruzi Tulahuen strain with a concentration similar to that displayed by the control drug benznidazole. Neq135 is tenfold lower kinetic affinity against hGAPDH and does not kill Balb-c fibroblast nor spleen mouse cells. These results emphasize the possibility of integrating ligand- and target-based designs to uncover potent and selective TcGAPDH inhibitors that expands the opportunity for further medicinal chemistry endeavor towards NAD(+) TcGAPDH site. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.029

文献信息

• Synthesis and characterization of new porphyrin/4-quinolone conjugates
  作者：Ana T.P.C. Gomes、Anna C. Cunha、Maria do Rosário M. Domingues、Maria G.P.M.S. Neves、Augusto C. Tomé、Artur M.S. Silva、Fernanda da C. Santos、Maria C.B.V. Souza、Vitor F. Ferreira、José A.S. Cavaleiro

  DOI：10.1016/j.tet.2011.07.025

  日期：2011.9

  New porphyrin/4-quinolone conjugates were synthesized from the Suzuki-Miyaura coupling reaction of a beta-borylated porphyrin with bromo-4-quinolones containing N-ethyl and N-D-ribofuranosyl substituents. The use of electrospray ionization tandem mass spectrometry showed important information about the fragmentation pathways of the new compounds. It was possible to distinguish between those compounds with the porphyrin moiety linked at the 6-position of the quinolone unit from their 7-substituted isomers. The new compounds showed to be good singlet oxygen generators. (C) 2011 Elsevier Ltd. All rights reserved.