8-羟基-1,6-萘啶-7-羧酸乙酯 | 410542-68-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 8-羟基-1,6-萘啶-7-羧酸乙酯
• 英文名称: 8-hydroxy-1,6-naphthyridine-7-carboxylic acid methyl ester
• 英文别名: methyl 8-hydroxy-1,6-naphthyridine-7-carboxylate
• CAS: 410542-68-6
• 化学式: C₁₀H₈N₂O₃
• 分子量: 204.185
• InChiKey: WDCSXBRXJCGXNG-UHFFFAOYSA-N

物化性质

• 沸点：
  465.3±40.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  8-羟基-1,6-萘啶-7-羧酸乙酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 21.0h， 生成 N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide
  参考文献：
  名称：

  Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties

  摘要：

  Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories. In spite of its remarkable potency and efficacy, unfortunately upon completion of phase I clinical studies, development of L-870,810 was halted. Because of its desirable pharmacological and pharmaceutical properties we were intrigued to design novel analogues of L-870,810 with goals to (1) improve upon limitations of naphthyridine-7-carboxamides as antiviral agents and (2) to reposition their use as innovative cytotoxic agents for cancer therapeutics. Herein, we report on the design and synthesis of a series of 1,6-naphthyridine-7-carboxamides with various substitutions at the 5- and 8-positions. All the new 5-substituted-8-hydroxy-[1,6]naphthyridines were potent IN inhibitors and the 5-substituted-8-amino-[1,6]naphthyridines were significantly cytotoxic. Further optimization of the 5,8-disubstituted-[1,6]naphthyridines with structural variation on 7-carboxamide delivered novel compounds with significant cytotoxicity in a panel of cancer cell lines and effective inhibition against select oncogenic kinases.

  DOI：

  10.1021/jm300667v
• 作为产物：
  描述：

  2-氯-3-吡啶甲醛 在 1,3-双(二苯基膦)丙烷 、 sodium ethanolate 、 palladium diacetate 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 100.0 ℃ 、517.12 kPa 条件下， 反应 51.0h， 生成 8-羟基-1,6-萘啶-7-羧酸乙酯
  参考文献：
  名称：

  Copper-Catalyzed C–N Coupling in the Synthesis of Integrase Inhibitors of Immunodeficiency Viruses

  摘要：

  This contribution describes the total synthesis of a complex macrocyclic integrase inhibitor, a key enzyme involved in the infection process of various immunodeficiency viruses. The key transformation of the synthetic strategy was the selective C-N coupling of a sulfonamide to a heteroaryl bromide in the presence of potentially competing amide and carbamate functionalities. The transformation was accomplished with CuI catalysis using bypiridine as the ligand in the presence of base and enabled a convergent approach to the target molecule.

  DOI：

  10.1021/op400228z
• 作为试剂：
  描述：

  methyl 5-chloro-8-[(4-methoxybenzyl)oxy]-1,6-naphthyridine-7-carboxylate 以 8-羟基-1,6-萘啶-7-羧酸乙酯 为溶剂， 生成 5-chloro-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide
  参考文献：
  名称：

  Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors

  摘要：

  描述了包括某些喹啉羧酰胺和萘啉羧酰胺衍生物在内的氮杂萘基羧酰胺衍生物。这些化合物是HIV整合酶的抑制剂和HIV复制的抑制剂，可用于预防或治疗HIV感染和治疗艾滋病，作为化合物或药学上可接受的盐，或作为药物组合物中的成分，可选择与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了预防、治疗或延缓艾滋病发作的方法，以及预防或治疗HIV感染的方法。

  公开号：

  US20030055071A1

文献信息

• [EN] NEUROLOGICALLY-ACTIVE COMPOUNDS<br/>[FR] COMPOSÉS NEUROLOGIQUEMENT ACTIFS
  申请人：PRANA BIOTECHNOLOGY LTD

  公开号：WO2004031161A1

  公开（公告）日：2004-04-15

  The present invention relates to neurologically-active compounds, being heterocyclic compounds having two fused 6-membered rings with a nitrogen atom at position 1 and a hydroxy or mercapto group at position 8 with at least one ring being aromatic. Also disclosed are processes for the preparation of these compounds and their use as pharmaceutical or veterinary agents, in particular for the treatment of neurological conditions, more specifically neurodegenerative conditions such as Alzheimer's disease.

  本发明涉及具有两个融合的6元环，其中第1位置有一个氮原子，第8位置有一个羟基或巯基基团的神经活性化合物，其中至少一个环是芳香环。还公开了制备这些化合物的方法以及它们作为药物或兽药剂的用途，特别是用于治疗神经系统疾病，更具体地说是神经退行性疾病，如阿尔茨海默病。
• Chemo-selective Suzuki–Miyaura reactions: Synthesis of highly substituted [1,6]-naphthyridines
  作者：Yadavalli Suneel Kumar、Fazlur-Rahman Nawaz Khan

  DOI：10.1016/j.cclet.2017.02.007

  日期：2017.7

  The Suzuki-Miyaura reaction of methyl-5-bromo-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (5), with 2 equiv. of arylboronic acids gave diarylated product, 5,8–diaryl-1,6-naphthyridine-7-carboxylate (7), whereas 1 equiv. of arylboronic acid resulted in site-selective formation of 5-aryl-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (8). The reactions proceeded with excellent chemo-selectivity in favor

  5-溴8-（甲苯磺酰氧基）-1,6-萘啶-7-羧酸甲酯（5）的Suzuki-Miyaura反应（2）。芳基硼酸的合成给出了二芳基化产物5,8-二芳基-1,6-萘啶-7-羧酸盐（7），而当量为1当量。芳基硼酸的过量导致5-芳基-8-（甲苯磺酰氧基）-1，6-萘啶-7-羧酸盐的位点选择性形成（8）。该反应以优异的化学选择性进行，有利于溴化物基团。同样，通过顺序添加与完全不同的硼酸进行一锅法反应，生成1，6-萘啶-7-羧酸盐（10），在5和8位含有两个不同的芳基。
• Identification and Optimization of a Series of 8-Hydroxy Naphthyridines with Potent <i>In Vitro</i> Antileishmanial Activity: Initial SAR and Assessment of <i>In Vivo</i> Activity
  作者：Michael G. Thomas、Manu De Rycker、Richard J. Wall、Daniel Spinks、Ola Epemolu、Sujatha Manthri、Suzanne Norval、Maria Osuna-Cabello、Stephen Patterson、Jennifer Riley、Frederick R. C. Simeons、Laste Stojanovski、John Thomas、Stephen Thompson、Claire Naylor、Jose M. Fiandor、Paul G. Wyatt、Maria Marco、Susan Wyllie、Kevin D. Read、Timothy J. Miles、Ian H. Gilbert

  DOI：10.1021/acs.jmedchem.0c00705

  日期：2020.9.10

  tolerated in vivo. Investigation of the mode of action (MoA) demonstrated that activity was driven by sequestration of divalent metal cations, a mechanism which was likely to drive the poor tolerability. This highlights the importance of investigating MoA and pharmacokinetics at an early stage for phenotypically active series.

  内脏利什曼病 (VL) 是一种寄生虫感染，每年导致大约 26 000-65 000 人死亡。可用的治疗方法受到毒性、疗效可变和不合适的剂量选择等问题的阻碍。迫切需要新的治疗方法，这导致了被忽视疾病药物计划(DND i )、葛兰素史克 (GSK) 和邓迪大学之间的合作。8-羟基萘啶被确定为起点，早期化合物在 VL 小鼠模型中表现出较弱的功效，但受到葡萄糖醛酸化的阻碍。解决这个问题的努力导致开发了具有改善体外特征的化合物，但这些化合物在体内耐受性差. 对作用方式 (MoA) 的研究表明，活性是由二价金属阳离子的螯合驱动的，这种机制可能导致耐受性差。这突出了在早期研究表型活性系列的 MoA 和药代动力学的重要性。
• 三取代咪唑并二氮杂萘酮化合物及其制备方 法和用途
  申请人：中国科学院上海药物研究所

  公开号：CN103709162B

  公开（公告）日：2016-12-07

  本发明涉及通式I所示的1,3,5‑三取代‑1H‑咪唑并[4,5‑h]1,6‑二氮杂萘‑2(3H)‑酮化合物、其异构体及药学上可接受的盐，其制备方法和用途以及包含所述化合物的组合物。本发明还涉及所述化合物、其异构体及药学上可接受的盐及含有其的组合物作为多靶点蛋白激酶抑制剂在制备用于治疗肿瘤疾病等与蛋白激酶特别是c‑Met有关的疾病的药物中的用途。
• [EN] AZA-QUINOLINOL PHOSPHONATE INTEGRASE INHIBITOR COMPOUNDS<br/>[FR] COMPOSES D'AZA-QUINOLINOL PHOSPHONATE INHIBITEURS DE L'INTEGRASE
  申请人：GILEAD SCIENCES INC

  公开号：WO2005028478A1

  公开（公告）日：2005-03-31

  Aza-quinolinol phosphonate compounds and methods for inhibition of HIV-integrase are disclosed. Formula (I). Ar is aryl or heteroaryl connecting R6 to L. L is a bond or a linker connecting a ring atom of Ar to N. The ring atoms, X1-X5 may be N, substituted nitrogen, or substituted carbon, and form rings. The compounds include at least one phosphonate group covalently attached at any site.

  本发明公开了一种Aza-quinolinol磷酸酯化合物及其抑制HIV整合酶的方法。其中，公式(I)中的Ar为芳基或杂环芳基，连接R6和L。L是连接Ar的环原子和N的键或连接链。环原子X1-X5可以是N、取代氮或取代碳，并形成环。这些化合物至少包括一个磷酸酯基固定在任何位点上。