N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide | 410544-56-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide
• 英文别名: 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide；5-bromo-N-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide
• CAS: 410544-56-8
• 化学式: C₁₆H₁₁BrFN₃O₂
• 分子量: 376.185
• InChiKey: VRVGOUHPADQNHC-UHFFFAOYSA-N

物化性质

• 沸点：
  644.8±55.0 °C(Predicted)
• 密度：
  1.636±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  75.1
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 储存条件：
  应存于室温、密闭且干燥的环境中。

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide 在 Cu₂O 吡啶 、 乙二胺四乙酸 、 三氟乙酸 作用下， 以 氯仿 、 水 为溶剂， 生成 5-(1,1-dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-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
• 作为产物：
  描述：

  2,3-吡啶二羧酸酐 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 magnesium sulfate 、 N,N-二甲基甲酰胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 48.0h， 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

文献信息

• Synthesis of Complex Phenols Enabled by a Rationally Designed Hydroxide Surrogate
  作者：Patrick S. Fier、Kevin M. Maloney

  DOI：10.1002/anie.201700244

  日期：2017.4.10

  The conversion of aryl halides to phenols under mild reaction conditions is a longstanding and formidable challenge in organic chemistry. Herein, we report the rational design of a broadly applicable Pd‐catalyzed method to prepare phenols with benzaldehyde oxime as a hydroxide surrogate. These reactions occur under mildly basic conditions and enable the late‐stage hydroxylation of several functionally‐dense

  在温和的反应条件下，芳基卤化物向苯酚的转化是有机化学领域一项长期而艰巨的挑战。本文中，我们报告了广泛适用的Pd催化方法的合理设计，该方法可使用苯甲醛肟作为氢氧化物替代物来制备苯酚。这些反应在温和的碱性条件下发生，可以使几种功能密集的药物样芳基卤化物发生后期羟基化反应。
• Chemistry informer libraries: a chemoinformatics enabled approach to evaluate and advance synthetic methods
  作者：Peter S. Kutchukian、James F. Dropinski、Kevin D. Dykstra、Bing Li、Daniel A. DiRocco、Eric C. Streckfuss、Louis-Charles Campeau、Tim Cernak、Petr Vachal、Ian W. Davies、Shane W. Krska、Spencer D. Dreher

  DOI：10.1039/c5sc04751j

  日期：——

  We report a standardized complex molecule diagnostic approach using collections of relevant drug-like molecules which we call chemistry informer libraries.

  我们报告了一种标准化的复杂分子诊断方法，使用我们称之为化学信息库的相关类药物分子集合。
• [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。
• Aza-quinolinol phosphonate integrase inhibitor compounds
  申请人：Jin Haolun

  公开号：US20050137199A1

  公开（公告）日：2005-06-23

  Aza-quinolinol phosphonate compounds and methods for inhibition of HIV-integrase are disclosed. Ar is aryl or heteroaryl connecting R 6 to L. L is a bond or a linker connecting a ring atom of Ar to N. The ring atoms, X 1 -X 5 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Aza-quinolinol磷酸酯化合物及其抑制HIV整合酶的方法。其中，Ar是芳基或杂芳基，连接R6到L。L是一个键或连接Ar的环原子到N的连接体。环原子X1-X5可以是N、取代氮或取代碳，并形成环。该化合物至少包括一个磷酸酯基固定在任何一个位点上。
• Phosphonate analogs of HIV integrase inhibitor compounds
  申请人：Cai R. Zhenhong

  公开号：US20060116356A1

  公开（公告）日：2006-06-01

  Novel HIV integrase inhibitor compounds having at least one phosphonate group, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.

  本发明揭示了至少具有一个膦酸酯基团的新型HIV整合酶抑制剂化合物，其保护中间体以及用于抑制HIV整合酶的方法。