4-氯-6-乙基喹啉 | 188758-77-2

• 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-氯-6-乙基喹啉
• 英文名称: 4-chloro-6-ethylquinoline
• CAS: 188758-77-2
• 化学式: C₁₁H₁₀ClN
• 分子量: 191.66
• InChiKey: VJTORLKSKVWEGQ-UHFFFAOYSA-N

物化性质

• 沸点：
  289.3±20.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-氯-6-乙基喹啉 在 硫酸 、 硝酸 作用下， 反应 0.33h， 以52%的产率得到4-chloro-6-ethyl-5-nitroquinoline
  参考文献：
  名称：

  Hypoxia-Selective Antitumor Agents. 15. Modification of Rate of Nitroreduction and Extent of Lysosomal Uptake by Polysubstitution of 4-(Alkylamino)-5-nitroquinoline Bioreductive Drugs

  摘要：

  Studies have shown that 4-(alkylamino)-5-nitroquinolines possess high selectivity (20-60-fold) for hypoxic tumor cells in vitro, but are not active as hypoxia-selective cytotoxins (HSCs) in vivo. The compounds show inadequate rates of extravascular diffusion, likely due both to sequestration of the bisbasic compounds into lysosomes and rapid nitroreduction. A further series of analogues, designed to counteract these limitations, has been synthesized and evaluated. Analogues bearing one to three electron-donating substituents on the quinoline have one-electron reduction potentials up to 100 mV lower than that of the unsubstituted compound (5), but do not have improved biological activity. The relationship between hypoxic selectivity and rates of metabolic reduction suggests at least two mechanisms of cytotoxicity for this series of 5-nitroquinolines. Compounds with high rates of reduction are toxic via oxygen-sensitive net bioreduction, while compounds which are poor substrates for nitroreduction are toxic through an oxygen-insensitive non-bioreductive mechanism. As rates of metabolic reduction are lowered, the non-bioreductive mechanism of toxicity becomes dominant and hypoxic selectivity is lost. A small series of analogues bearing hydrophilic but neutral side chains were also prepared. Compounds with a dihydroxypropyl side chain retained cytotoxic potency and hypoxic cell selectivity in cell culture assays, and had lowered uptake into lysosomes, but none of three analogues evaluated against KHT tumors in mice showed activity as an HSC in vivo.

  DOI：

  10.1021/jm9607865
• 作为产物：
  描述：

  6-乙基-4-羟基喹啉-3-羧酸 在 二苯甲酮 、 三氯氧磷 作用下， 生成 4-氯-6-乙基喹啉
  参考文献：
  名称：

  Hypoxia-Selective Antitumor Agents. 15. Modification of Rate of Nitroreduction and Extent of Lysosomal Uptake by Polysubstitution of 4-(Alkylamino)-5-nitroquinoline Bioreductive Drugs

  摘要：

  Studies have shown that 4-(alkylamino)-5-nitroquinolines possess high selectivity (20-60-fold) for hypoxic tumor cells in vitro, but are not active as hypoxia-selective cytotoxins (HSCs) in vivo. The compounds show inadequate rates of extravascular diffusion, likely due both to sequestration of the bisbasic compounds into lysosomes and rapid nitroreduction. A further series of analogues, designed to counteract these limitations, has been synthesized and evaluated. Analogues bearing one to three electron-donating substituents on the quinoline have one-electron reduction potentials up to 100 mV lower than that of the unsubstituted compound (5), but do not have improved biological activity. The relationship between hypoxic selectivity and rates of metabolic reduction suggests at least two mechanisms of cytotoxicity for this series of 5-nitroquinolines. Compounds with high rates of reduction are toxic via oxygen-sensitive net bioreduction, while compounds which are poor substrates for nitroreduction are toxic through an oxygen-insensitive non-bioreductive mechanism. As rates of metabolic reduction are lowered, the non-bioreductive mechanism of toxicity becomes dominant and hypoxic selectivity is lost. A small series of analogues bearing hydrophilic but neutral side chains were also prepared. Compounds with a dihydroxypropyl side chain retained cytotoxic potency and hypoxic cell selectivity in cell culture assays, and had lowered uptake into lysosomes, but none of three analogues evaluated against KHT tumors in mice showed activity as an HSC in vivo.

  DOI：

  10.1021/jm9607865

文献信息

• [EN] COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS DISEASE<br/>[FR] COMPOSÉ POUR LE TRAITEMENT ET LA PROPHYLAXIE DE LA MALADIE DU VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013020993A1

  公开（公告）日：2013-02-14

  A compound of formula (I), as well as pharmaceutically acceptable salt thereof, wherein R1 to R10, A, Q, X and Y are as defined in description and in claims, can be used as a medicament for the treatment of respiratory syncytial virus.

  式（I）的化合物，以及其药学上可接受的盐，其中R1至R10，A，Q，X和Y如描述和索赔中定义的，可用作治疗呼吸道合胞病毒的药物。
• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102311A1

  公开（公告）日：2020-04-02

  Bridged compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. wherein R 2 , R 3 R 4 , R 5 and R 6 are defined herein.

  桥接化合物，其结构式为(I)和(II)，包含它们的药物组合物，制造它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、障碍和状况的方法，如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、难治性抑郁、焦虑性抑郁、双相情感障碍）、癌症和眼科疾病相关的方法。 其中R2、R3、R4、R5和R6的定义如下。
• COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS DISEASE
  申请人：Chen Li

  公开号：US20130196974A1

  公开（公告）日：2013-08-01

  A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R 1 to R 10 , A, Q, X and Y are as defined in the specification and claims, and their use as a pharmaceutical for the treatment or prophylaxis of respiratory syncytial virus disease.

  一种化合物的公式（I），以及其药学上可接受的盐，其中R1至R10，A，Q，X和Y的定义如规范和索赔中所述，以及其作为药物用于治疗或预防呼吸道合胞病毒疾病的用途。
• US8871756B2
  申请人：——

  公开号：US8871756B2

  公开（公告）日：2014-10-28
• Hypoxia-Selective Antitumor Agents. 15. Modification of Rate of Nitroreduction and Extent of Lysosomal Uptake by Polysubstitution of 4-(Alkylamino)-5-nitroquinoline Bioreductive Drugs
  作者：Bronwyn G. Siim、Graham J. Atwell、Robert F. Anderson、Peter Wardman、Susan M. Pullen、William R. Wilson、William A. Denny

  DOI：10.1021/jm9607865

  日期：1997.4.1

  Studies have shown that 4-(alkylamino)-5-nitroquinolines possess high selectivity (20-60-fold) for hypoxic tumor cells in vitro, but are not active as hypoxia-selective cytotoxins (HSCs) in vivo. The compounds show inadequate rates of extravascular diffusion, likely due both to sequestration of the bisbasic compounds into lysosomes and rapid nitroreduction. A further series of analogues, designed to counteract these limitations, has been synthesized and evaluated. Analogues bearing one to three electron-donating substituents on the quinoline have one-electron reduction potentials up to 100 mV lower than that of the unsubstituted compound (5), but do not have improved biological activity. The relationship between hypoxic selectivity and rates of metabolic reduction suggests at least two mechanisms of cytotoxicity for this series of 5-nitroquinolines. Compounds with high rates of reduction are toxic via oxygen-sensitive net bioreduction, while compounds which are poor substrates for nitroreduction are toxic through an oxygen-insensitive non-bioreductive mechanism. As rates of metabolic reduction are lowered, the non-bioreductive mechanism of toxicity becomes dominant and hypoxic selectivity is lost. A small series of analogues bearing hydrophilic but neutral side chains were also prepared. Compounds with a dihydroxypropyl side chain retained cytotoxic potency and hypoxic cell selectivity in cell culture assays, and had lowered uptake into lysosomes, but none of three analogues evaluated against KHT tumors in mice showed activity as an HSC in vivo.