7-bromo-1,4-dihydro-4-oxo-1-(β-D-ribofuranosyl)quinoline-3-carboxylic acid | 224175-74-0

• 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: 7-bromo-1,4-dihydro-4-oxo-1-(β-D-ribofuranosyl)quinoline-3-carboxylic acid
• 英文别名: 7-bromo-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-4-oxo-quinoline-3-carboxylic acid；7-bromo-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 224175-74-0
• 化学式: C₁₅H₁₄BrNO₇
• 分子量: 400.183
• InChiKey: NGAYUIJOWNVTRB-FMKGYKFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  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

文献信息

• Molecular design, synthesis and biological evaluation of 1,4-dihydro-4-oxoquinoline ribonucleosides as TcGAPDH inhibitors with trypanocidal activity
  作者：Fabyana A. Soares、Renata Sesti-Costa、João Santana da Silva、Maria Cecília B.V. de Souza、Vitor F. Ferreira、Fernanda da C. Santos、Patricia A.U. Monteiro、Andrei Leitão、Carlos A. Montanari

  DOI：10.1016/j.bmcl.2013.06.029

  日期：2013.8

  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.