5-氧代-1H-喹啉-3-羧酸 | 911108-90-2

• 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
• 中文名称: 5-氧代-1H-喹啉-3-羧酸
• 英文名称: 5-hydroxyquinoline-3-carboxylic acid
• CAS: 911108-90-2
• 化学式: C₁₀H₇NO₃
• 分子量: 189.17
• InChiKey: LJZUCCGYBXJMDF-UHFFFAOYSA-N

物化性质

• 熔点：
  >260 °C
• 沸点：
  426.7±30.0 °C(Predicted)
• 密度：
  1.480±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  5-氧代-1H-喹啉-3-羧酸 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-{2-[2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[(5-hydroxy-quinoline-3-carbonyl)-amino]-hexanoylamino}-N-(1-carbamoyl-2-phenyl-ethyl)-succinamic acid; hydrate
  参考文献：
  名称：

  Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N.epsilon.)-amide residues

  摘要：

  A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(N(epsilon)-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-AT receptor agonists. These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series. A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group of the lysine did not affect affinity for the CCK-AT receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor. The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked by selective CCK-A receptor antagonists.

  DOI：

  10.1021/jm00089a010
• 作为产物：
  描述：

  在 氢溴酸 作用下， 以 水 为溶剂， 以80%的产率得到5-氧代-1H-喹啉-3-羧酸
  参考文献：
  名称：

  Rational design of carbamate-based dual binding site and central AChE inhibitors by a “biooxidisable” prodrug approach: Synthesis, in vitro evaluation and docking studies

  摘要：

  Herein, we report a new class of dual binding site AChE inhibitor 4 designed to exert a central cholinergic activation thanks to a redox-activation step of a prodrug precursor 3. Starting from potent pseudo irreversible quinolinium salts AChE inhibitors 2 previously reported, a new set of diversely substituted quinolinium salts 2a-p was prepared and assayed for their inhibitory activity against AChE. Structure activity relationship (SAR) analysis of 2a-p coupled with molecular docking studies allowed us to determine which position of the quinolinium scaffold may be considered to anchor the phtalimide fragment presumed to interact with the peripheral anionic site (PAS). In addition, molecular docking provided insight on the linker length required to connect both quinolinium and phatlimide moieties without disrupting the crucial role of quinolinium salt moiety within the catalytic active site (CAS); namely placing the carbamate in the correct position to trigger carbamylation of the active-site serine hydroxyl. Based on this rational design, the putative dual binding site inhibitor 4 and its prodrug 3 were synthesized and subsequently evaluated in vitro against AChE. Pleasingly, whereas compound 4 showed to be a highly potent inhibitor of AChE (IC50 = 6 nM) and binds to AChE-PAS to the same extent as donepezil, its prodrug 3 revealed to be inactive (IC50> 10 mu M). These preliminary results constitute one of the few examples of carbamate-based dual binding site AChE inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.057

文献信息

• Rational design of central selective acetylcholinesterase inhibitors by means of a “bio-oxidisable prodrug” strategy
  作者：Pierre Bohn、Nicolas Le Fur、Guillaume Hagues、Jean Costentin、Nicolas Torquet、Cyril Papamicaël、Francis Marsais、Vincent Levacher

  DOI：10.1039/b903041g

  日期：——

  oxidation of an N-alkyl-1,4-dihydroquinoline 1 to the corresponding quinolinium salt 2 unmasking the positive charge required for binding to the catalytic anionic site of the enzyme. The synthesis of a set of 1,4-dihydroquinolines 1 and their corresponding quinolinium salts 2 is presented. An in vitro biological evaluation revealed that while all reduced forms 1 were unable to exhibit any anticholinesterase

  这项工作涉及开发新的中央选择性乙酰胆碱酯酶抑制剂的“生物可氧化前药”策略的设计。预期该前药方法会降低外周抗胆碱酯酶活性，从而导致目前市售的各种副作用疼痛抑制剂。这些新的设计疼痛 抑制剂 喹啉 系列大致基于的循环类似物 利凡斯的明。前药的关键活化步骤涉及N-烷基-1，4-二氢喹啉1氧化为相应的喹啉鎓盐2，从而掩盖了与酶的催化阴离子位点结合所需的正电荷。介绍了一组1,4-二氢喹啉1及其相应的喹啉鎓盐2的合成。的体外生物学评价显示，虽然所有的还原形式1无法表现出任何抗胆碱酯酶活性（IC 50 > 10 6 nm）时，大部分的喹啉盐的2显示高疼痛抑制活性（IC 50为6μM至7 nM）。这些初步的体外试验验证了这些环状类似物的使用。利凡斯的明喹啉系列的药物作为进一步在体内开发这种“生物可氧化前药”方法的诱人化学工具。
• HETEROCYCLIC COMPOUNDS, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS, IN PARTICULAR AS ANTI-ALZHEIMER AGENTS
  申请人：Marsais Francis

  公开号：US20090062279A1

  公开（公告）日：2009-03-05

  The invention is related to compound which comprises at least one radical C═Y, Y being O or S, and an oxidable and non protonable nitrogen atom N wherein the distance (d) between the at least one carbon atom of the radical group C═Y and the nitrogen atom, when oxidized, is comprised between 0.3 and 0.8 nanometers. The invention is related to new heterocyclic compounds defined by formula G, their preparation, to pharmaceutical compositions comprising them and to their use as therapeutic agents, particularly in the treatment of neurodegenerative or Alzheimer disease.

  本发明涉及一种化合物，其包含至少一个基团C═Y，其中Y为O或S，以及一个可氧化且不可质子化的氮原子N，其中在氧化时，基团C═Y的至少一个碳原子与氮原子之间的距离(d)在0.3至0.8纳米之间。本发明涉及由公式G定义的新杂环化合物及其制备方法，涉及包含它们的制药组合物以及它们在治疗神经退行性或阿尔茨海默病方面的用途。
• WO2006/103120
  申请人：——

  公开号：——

  公开（公告）日：——
• NEW HETEROCYCLIC COMPOUNDS, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS, IN PARTICULAR AS ANTI-ALZHEIMER AGENTS
  申请人：Insa Rouen

  公开号：EP1868998A2

  公开（公告）日：2007-12-26
• US7977354B2
  申请人：——

  公开号：US7977354B2

  公开（公告）日：2011-07-12