ethyl 6-bromo-1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-quinolone-3-carboxylate | 224175-70-6

• 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 6-bromo-1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-quinolone-3-carboxylate
• CAS: 224175-70-6
• 化学式: C₃₈H₃₀BrNO₁₀
• 分子量: 740.561
• InChiKey: PTULAMAFOBQPNC-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：

  ethyl 6-bromo-1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-quinolone-3-carboxylate 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成 ethyl 6-bromo-1-(β-D-ribofuranosyl)-4-quinolone-3-carboxylate
  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：

  6-溴-4-羟基-3-喹啉羧酸乙酯 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 ethyl 6-bromo-1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-quinolone-3-carboxylate
  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 Antiproliferative Activity of Quinolone Nucleosides Against the Human Myelogenous Leukemia K‐562 Cell Line
  作者：Lena Wicke、Joachim W. Engels、Roberto Gambari、Antoine M. Saab

  DOI：10.1002/ardp.201300232

  日期：2013.10

  quinolone nucleosides linked to aniline or phenol via N or O heteroatom‐bridges presenting new compounds were synthesized by palladium‐catalyzed Buchwald–Hartwig cross‐coupling reactions. 6‐Bromoquinolone nucleoside precursors, being protected by either benzoyl or TBDMS protecting groups on the ribose moiety, were subjected to different Buchwald–Hartwig conditions as the key step. Defined deprotection

  通过钯催化的 Buchwald-Hartwig 交叉偶联反应合成了一组通过 N 或 O 杂原子桥与苯胺或苯酚连接的 6-取代喹诺酮核苷，呈现出新的化合物。6-溴喹诺酮核苷前体被核糖部分上的苯甲酰基或 TBDMS 保护基团保护，作为关键步骤经受不同的 Buchwald-Hartwig 条件。确定的脱保护步骤以良好的产率获得在 3 位带有酯、酸或酰胺官能团的最终目标化合物。因此，通过收敛合成路线获得了一系列新型喹诺酮核苷衍生物。人类慢性粒细胞白血病 K562 细胞的生物学测试对其中两种细胞发挥有效的抗增殖活性，但不诱导分化。
• Synthesis of new porphyrin/4-quinolone conjugates and evaluation of their efficiency in the photoinactivation of Staphylococcus aureus
  作者：Pedro N. Batalha、Ana T. P. C. Gomes、Luana S. M. Forezi、Liliana Costa、Maria Cecília B. V. de Souza、Fernanda da C. S. Boechat、Vitor F. Ferreira、Adelaide Almeida、Maria A. F. Faustino、Maria G. P. M. S. Neves、José A. S. Cavaleiro

  DOI：10.1039/c5ra11070j

  日期：——

  The synthesis of new porphyrin/4-quinolone conjugates and their evaluation as potential photosensitizers in the photoinactivation of Staphylococcus aureus is described.

  本文描述了合成新的卟啉/4-喹啉共轭物并评估其作为潜在光敏剂在光灭活金黄色葡萄球菌方面的应用。
• 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.