4-羟基-7-氰基喹啉 | 860205-30-7

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 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: 4-羟基-7-氰基喹啉
• 英文名称: 4-hydroxyquinoline-7-carbonitrile
• 英文别名: 4-Hydroxy-7-cyanoquinoline；4-oxo-1H-quinoline-7-carbonitrile
• CAS: 860205-30-7
• 化学式: C₁₀H₆N₂O
• mdl: MFCD18803146
• 分子量: 170.17
• InChiKey: RLPFPQFPWYYNOP-UHFFFAOYSA-N

物化性质

• 沸点：
  402.7±25.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-羟基-7-氰基喹啉 在 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 4-(methylamino)quinolin-7-carbonitrile
  参考文献：
  名称：

  Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods

  摘要：

  In order to probe structure-activity relationships of association with ferriprotoporphyrin IX (logK) and inhibition of beta-hematin formation, a series of 4-aminoquinolines with varying substituents at the 7-position (X) have been synthesized. These have been further elaborated by introduction of two different R groups on the 4-amino nitrogen atom in the form of methyl (R = Me) and ethylamine (R = EtNH2) side chains. Data for a previously investigated series containing an N,N-diethyl-ethylamine side chain were also compared with the findings of this study. Experimentally, logK values for the simple 4-aminoquinoline series (R = H) were found to correlate with the hydrophobicity constant (pi) of the group X. The logK values for the series with R = Me and EtNH2 were found to correlate with those of the series with R = H. The log of the 50% beta-hematin inhibitory activity (log BHIA(50)) was found to correlate with logK and either meta (sigma(m)) or para (sigma(p)) Hammett constants for the series with R = Me and EtNH2, but not the simple series with R = H. To further improve predictability, correlations with ab initio electrostatic parameters, namely Mulliken and CHelpG charges were investigated. The best correlations were found with CHelpG charges which indicated that logK values can be predicted from the charges on atom H-8 and the group X in the quinolinium species computed in vacuum, while log BHIA50 values can be predicted from the CHelpG charges on C-7, C-8 and N-1 for the neutral species in vacuum. These correlations indicate that association and inhibition of beta-hematin formation are separately determined. They also suggest that electron withdrawing groups at the 7-position, but not necessarily hydrophobic groups are required for hemozoin inhibition. The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.040
• 作为产物：
  描述：

  对氰基苯乙酮 在 盐酸 、 silver tetrafluoroborate 、 carbonyl(pentamethylcyclopentadienyl)cobalt diiodide 作用下， 以 水 、 甲苯 为溶剂， 反应 21.0h， 生成 4-羟基-7-氰基喹啉
  参考文献：
  名称：

  Co(III)-Catalyzed Enaminone-Directed C–H Amidation for Quinolone Synthesis

  摘要：

  We report herein the development of a Co (III)-catalyzed enaminone-directed C-H amidation method for synthetic access to quinolones, an important heterocyclic scaffold for diverse pharmaceutically active structures. The C-H coupling with,dioxazolones and subsequent deacylation of an installed amide group allow consecutive C-N coupling generation of quinolones with wide-ranging compatible substituent patterns.

  DOI：

  10.1021/acs.orglett.7b00968

文献信息

• [EN] HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES
  申请人：PI INDUSTRIES LTD

  公开号：WO2018116072A1

  公开（公告）日：2018-06-28

  The present invention relates to compounds of the general formula (1) wherein the variables are defined as given in the description and claims. The invention further relates to uses of and to, processes and intermediates related to compounds of the general formula (I), wherein Q is wherein the substituents of I, Ia and Ib are as defined in description and claims.

  本发明涉及通式（1）的化合物，其中变量的定义如描述和权利要求中所述。本发明还涉及通式（I）的化合物的用途、相关的工艺和中间体，其中Q是I、Ia和Ib的取代基，如描述和权利要求中所定义的。
• Regioselective Synthesis of Quinolin-4-ones by Pyrolysis of Anilinomethylene Derivatives of Meldrum’s Acid
  作者：Hamish McNab、Lawrence Hill、S. Imam、William O’Neill

  DOI：10.1055/s-0029-1217383

  日期：2009.7

  Electron-rich and electron-deficient anilinomethylene derivatives of Meldrum’s acid cyclize equally efficiently to quinolin-4-ones via imidoylketene intermediates under flash vacuum pyrolysis (FVP) conditions.

  在闪速真空热解（FVP）条件下，梅氏酸的富电子和缺电子苯胺亚甲基衍生物通过亚胺酰基乙烯中间体环化成喹啉-4-酮的效率相同。
• Co(III)-Catalyzed Enaminone-Directed C–H Amidation for Quinolone Synthesis
  作者：Pengfei Shi、Lili Wang、Kehao Chen、Jie Wang、Jin Zhu

  DOI：10.1021/acs.orglett.7b00968

  日期：2017.5.5

  We report herein the development of a Co (III)-catalyzed enaminone-directed C-H amidation method for synthetic access to quinolones, an important heterocyclic scaffold for diverse pharmaceutically active structures. The C-H coupling with,dioxazolones and subsequent deacylation of an installed amide group allow consecutive C-N coupling generation of quinolones with wide-ranging compatible substituent patterns.
• Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods
  作者：Samkele Nsumiwa、David Kuter、Sergio Wittlin、Kelly Chibale、Timothy J. Egan

  DOI：10.1016/j.bmc.2013.04.040

  日期：2013.7

  In order to probe structure-activity relationships of association with ferriprotoporphyrin IX (logK) and inhibition of beta-hematin formation, a series of 4-aminoquinolines with varying substituents at the 7-position (X) have been synthesized. These have been further elaborated by introduction of two different R groups on the 4-amino nitrogen atom in the form of methyl (R = Me) and ethylamine (R = EtNH2) side chains. Data for a previously investigated series containing an N,N-diethyl-ethylamine side chain were also compared with the findings of this study. Experimentally, logK values for the simple 4-aminoquinoline series (R = H) were found to correlate with the hydrophobicity constant (pi) of the group X. The logK values for the series with R = Me and EtNH2 were found to correlate with those of the series with R = H. The log of the 50% beta-hematin inhibitory activity (log BHIA(50)) was found to correlate with logK and either meta (sigma(m)) or para (sigma(p)) Hammett constants for the series with R = Me and EtNH2, but not the simple series with R = H. To further improve predictability, correlations with ab initio electrostatic parameters, namely Mulliken and CHelpG charges were investigated. The best correlations were found with CHelpG charges which indicated that logK values can be predicted from the charges on atom H-8 and the group X in the quinolinium species computed in vacuum, while log BHIA50 values can be predicted from the CHelpG charges on C-7, C-8 and N-1 for the neutral species in vacuum. These correlations indicate that association and inhibition of beta-hematin formation are separately determined. They also suggest that electron withdrawing groups at the 7-position, but not necessarily hydrophobic groups are required for hemozoin inhibition. The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible. (C) 2013 Elsevier Ltd. All rights reserved.