7-chloro-3-fluoroquinoline

• 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
• 英文名称: 7-chloro-3-fluoroquinoline
• 英文别名: 7-Chloro-3-fluoroquinoline
• 化学式: C₉H₅ClFN
• 分子量: 181.597
• InChiKey: JDNSQXAVXYZSPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  12
• 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：
  12.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-chloro-3-fluoroquinoline 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate 、 palladium diacetate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 反应 6.0h， 生成 N¹-(1-adamantylmethyl)-N³-(7-chloro-3-fluoroquinolin-4-yl)butane-1,3-diamine
  参考文献：
  名称：

  Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

  摘要：

  The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.

  DOI：

  10.1021/acs.jmedchem.5b01374
• 作为产物：
  描述：

  7-氯-4-羟基喹啉 在 tetrafluoroboric acid 、 水 、 硝酸 、 丙酸 、 tin(ll) chloride 、 sodium hydroxide 、 sodium nitrite 、 三氯氧磷 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 46.0h， 生成 7-chloro-3-fluoroquinoline
  参考文献：
  名称：

  Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

  摘要：

  The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.

  DOI：

  10.1021/acs.jmedchem.5b01374

文献信息

• Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?
  作者：Natasa Terzić、Jelena Konstantinović、Mikloš Tot、Jovana Burojević、Olgica Djurković-Djaković、Jelena Srbljanović、Tijana Štajner、Tatjana Verbić、Mario Zlatović、Marta Machado、Inês S. Albuquerque、Miguel Prudêncio、Richard J. Sciotti、Stevan Pecic、Sarah D’Alessandro、Donatella Taramelli、Bogdan A. Šolaja

  DOI：10.1021/acs.jmedchem.5b01374

  日期：2016.1.14

  The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.