ethyl 1-[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]-6-methyl-4-oxoquinoline-3-carboxylate | 176696-99-4

• 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: ethyl 1-[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]-6-methyl-4-oxoquinoline-3-carboxylate
• CAS: 176696-99-4
• 化学式: C₃₉H₃₃NO₁₀
• 分子量: 675.692
• InChiKey: MRRYNUZFJUTIHU-HYGOWAQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.69
• 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：
  0.21
• 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：

  ethyl 1-[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]-6-methyl-4-oxoquinoline-3-carboxylate 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  固定在磁性颗粒上的核苷水解酶作为抑制剂的流式筛选和表征工具

  摘要：

  核苷水解酶 (NH) 被认为是开发新型抗原虫剂的目标。用于鉴定 NH 抑制剂的新型自动化筛选方法的开发可以加速药物发现过程的第一阶段。在这项工作中，来自杜氏利什曼原虫的 NH(LdNH) 被共价固定到磁性颗粒 (LdNH-MPs) 上，并被磁铁捕获到 TFE 管中，形成固定化酶反应器 (IMER)。对于自动测定，Ld NH-MP-IMER 串联连接至 HPLC-DAD 系统中的分析柱，通过产物次黄嘌呤的定量来监测酶活性。动力学研究得出肌苷底物的K M值为 2079 ± 87 µmol.L-1使用含有 12 种喹诺酮核糖核苷的文库对LdNH-MP-IMER 进行流动筛选验证。其中，3个被鉴定为新型竞争性LdNH抑制剂，Ki值在83.5至169.4 µmol.L-1。这种新颖的在线筛选测定已被证明可靠、快速、低成本，并且适用于大型化合物库。

  DOI：

  10.1016/j.jpba.2023.115589
• 作为产物：
  描述：

  2-(对甲苯氨基亚甲基)丙二酸二乙酯 在 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 、 N,O-双(三甲基硅烷基)三氟乙酰胺 作用下， 以 various solvent(s) 为溶剂， 反应 8.15h， 生成 ethyl 1-[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]-6-methyl-4-oxoquinoline-3-carboxylate
  参考文献：
  名称：

  Nucleosides Having Quinolone Derivatives as Nitrogenated Base: Regiospecific and Stereospecific Ribosylation of 3-Carbethoxy-1,4-dihydro-4-oxoquinolines

  摘要：

  Ribosylation reactions of previously silylated 3-carbethoxy-8-methyl-1,4-dilhydro-4-oxoquinoline (6a) and 3-carbethoxy-6-methyl-1,4-dihydro-4-oxoquinoline (6b) with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (7), under Lewis acid catalysis, were studied. The method using hexamethyldisilazane (HMDS)/trimethylchlorosilane (TMCS) mixture for silylation and anhydrous stannic chloride as catalyst for ribosylation failed to give any nucleoside product. On the other hand, the protected nucleoside 3-carbethoxy-6-methyl-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-dihydro-4-oxoquinoline (8b) was obtained in good yields using bis(trimethylsilyl)trifluoroacetamide (BSTFA) containing 1% of TMCS and the same catalyst. Compound 8b was more easily isolated in higher yields with an improvement of the later method by replacing stannic chloride with trimethylsilyl trifluoromethanesulfonate (TMSOTf).De-O-benzoylation of 8b with methanolic sodium hydroxide solution afforded the free riboside 3-carbomethoxy-6-methyl-1-beta-D-ribofuranosyl-1,4-dihydro-4-oxoquinoline (9b). The structures of the obtained products were confirmed by their UV, MS IR, H-1 and C-13-NMR data.

  DOI：

  10.1080/07328319608002135

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.