6-chloro-1,4-dihydro-4-oxo-1-(β-D-ribofuranosyl)quinoline-3-carboxylic acid | 224175-73-9

• 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: 6-chloro-1,4-dihydro-4-oxo-1-(β-D-ribofuranosyl)quinoline-3-carboxylic acid
• 英文别名: 6-chloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 224175-73-9
• 化学式: C₁₅H₁₄ClNO₇
• 分子量: 355.732
• InChiKey: IFFPNCKBDBQCNL-FMKGYKFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 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：

  1-(3,4-Bis-benzoyloxy-5-benzoyloxymethyl-tetrahydro-furan-2-yl)-6-chloro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 6-chloro-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

• ISATIN-DERIVED COMPOUNDS, USE OF THE COMPOUNDS FOR THE TREATMENT OF AIDS AND METHOD OF TREATMENT USING THESE COMPOUNDS
  申请人：Fundação Oswaldo Cruz (fiocruz) - Superintendência De Planejamento

  公开号：EP3456718A1

  公开（公告）日：2019-03-20

  This invention relates to HIV-inhibiting compounds consisting of other Formulae I, II or III isatin derivatives, as shown below (Formulae I, II and III), whereby in Formulae I, II and III, R1 is selected from H, CH3 or Cl; R2 is selected from one of the following radicals: zidovudine, amprenavir or an acyclic phosphonate chain, as shown below. This invention also relates to the use and treatment method using the Formulae I, II and III compounds. According to this invention, these compounds are also used for the treatment of infections caused by HBV or co-infection caused by HIV and HBV.

  本发明涉及由下式（式Ⅰ、式Ⅱ和式Ⅲ）所示的其他式Ⅰ、式Ⅱ或式Ⅲ异atin衍生物组成的HIV抑制化合物，其中在式Ⅰ、式Ⅱ和式Ⅲ中，R1选自H、CH3或Cl；R2选自如下基团之一：齐多夫定、安普那韦或无环膦酸链，如下所示。本发明还涉及使用式 I、II 和 III 化合物的用途和治疗方法。根据本发明，这些化合物还可用于治疗由 HBV 引起的感染或由 HIV 和 HBV 引起的合并感染。
• ISATIN-DERIVED COMPOUNDS, USE OF THE COMPOUNDS FOR THE TREATMENT OF AIDS AND HBV INFECTIONS
  申请人：Fundação Oswaldo Cruz

  公开号：EP3456718B1

  公开（公告）日：2021-02-17
• [EN] ISATIN-DERIVED COMPOUNDS, USE OF THE COMPOUNDS FOR THE TREATMENT OF AIDS AND METHOD OF TREATMENT USING THESE COMPOUNDS<br/>[FR] COMPOSÉS DÉRIVÉS D'ISATINE, UTILISATION DE CES COMPOSÉ DANS LE TRAITEMENT DU SIDA ET MÉTHODE DE TRAITEMENT FAISANT APPEL AUXDITS COMPOSÉS<br/>[PT] COMPOSTOS DERIVADOS DE ISATINA, USO DOS COMPOSTOS NO TRATAMENTO DE AIDS E MÉTODO DE TRATAMENTO USANDO DITOS COMPOSTOS
  申请人：FUNDAÇÃO OSWALDO CRUZ (FIOCRUZ) - SUPERINTENDÊNCIA DE PLANEJAMENTO

  公开号：WO2017193180A1

  公开（公告）日：2017-11-16

  A presente invenção se refere a compostos inibidores do HIV consistindo de derivados de isatina de fórmulas I, II e III, conforme representados a seguir (fórmulas I, II e III) onde nas fórmulas I, II e III, R1 é selecionado dentre H, CH3 ou Cl R2 é selecionado dentre um dos seguintes radicais: zidovudina, amprenavir ou uma cadeia fosfonato acíclica, representados a seguir. A presente invenção também consiste do uso e do método de tratamento usando os compostos de fórmulas I, II e III. Os compostos da presente invenção também são usados no tratamento de uma infecção causada pelo HBV ou na coinfecção causada pelo HIV e HBV.