5-氯-2,6-二甲氧基-4-甲基-8-硝基喹啉 | 189746-21-2

• 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: 5-氯-2,6-二甲氧基-4-甲基-8-硝基喹啉
• 英文名称: 5-chloro-2,6-dimethoxy-4-methyl-8-nitro-quinoline
• 英文别名: 5-chloro-2,6-dimethoxy-4-methyl-8-nitroquinoline；8-nitro-2,6-dimethoxy-5-chloro-4-methylquinoline
• CAS: 189746-21-2
• 化学式: C₁₂H₁₁ClN₂O₄
• 分子量: 282.683
• InChiKey: VZVNAHCSVNVONJ-UHFFFAOYSA-N

物化性质

• 熔点：
  200-201 °C
• 沸点：
  429.0±40.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  77.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-氯-2,6-二甲氧基-4-甲基-8-硝基喹啉 在 10% palladium on activated carbon 、 四丁基溴化铵 、 氢气 、 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 生成 8-amino-2,6-dimethoxy-4-methyl-5-(4-trifluoromethylphenyl)-quinoline
  参考文献：
  名称：

  Antimalarial Activity of Novel 5-Aryl-8-Aminoquinoline Derivatives

  摘要：

  In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivative, was prepared and assessed for antimalarial activities The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 mm, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone Analogues with electron donating groups showed better activity than those with electron withdrawing substituents Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC50 data The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests

  DOI：

  10.1021/jm100911f
• 作为产物：
  描述：

  2-氯-6-甲氧基-4-甲基-喹啉 在 磺酰氯 、 四磷十氧化物 作用下， 以 甲醇 、 磷酸三乙酯 、 溶剂黄146 为溶剂， 反应 44.75h， 生成 5-氯-2,6-二甲氧基-4-甲基-8-硝基喹啉
  参考文献：
  名称：

  Antimalarial Activity of Novel 5-Aryl-8-Aminoquinoline Derivatives

  摘要：

  In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivative, was prepared and assessed for antimalarial activities The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 mm, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone Analogues with electron donating groups showed better activity than those with electron withdrawing substituents Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC50 data The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests

  DOI：

  10.1021/jm100911f

文献信息

• Process for the preparation of anti-malarial drugs
  申请人：SmithKline Beecham p.l.c.

  公开号：US06479660B1

  公开（公告）日：2002-11-12

  The invention relates to novel intermediates and processes for the preparation of quinoline compounds useful as anti-malarial drugs and novel intermediates useful in the process. A process for the preparation of a compound of formula (I) in which R1 is C1-6 alkyl; R2 and R3 are independently hydrogen, halogen, trifluoromethyl or C1-6 alkoxy; R4 is C1-6 alkyl; R5 is hydrogen or C1-6 alkyl; and R6 or amino which comprises reacting a compound of formula (II) in which R1, R4 and R5 are as defined in formula (I) and X is a leading group with a compound of formula (III).

  该发明涉及一种新型中间体和制备喹啉化合物的过程，该化合物可用作抗疟疾药物，以及在该过程中有用的新型中间体。一种制备式（I）化合物的方法，其中R1为C1-6烷基；R2和R3分别为氢、卤素、三氟甲基或C1-6烷氧基；R4为C1-6烷基；R5为氢或C1-6烷基；以及R6或氨基，包括将式（II）化合物与式（III）化合物反应，其中式（II）中的R1、R4和R5如式（I）中定义，X为引导基。
• [EN] PROCESS FOR THE PREPARATION OF ANTI-MALARIAL DRUGS<br/>[FR] PROCEDE DE PREPARATION DE MEDICAMENTS ANTI-PALUDIQUES
  申请人：SMITHKLINE BEECHAM P.L.C.

  公开号：WO1997013753A1

  公开（公告）日：1997-04-17

  (EN) The invention relates to novel intermediates and processes for the preparation of quinoline compounds useful as anti-malarial drugs and novel intermediates useful in the process. A process for the preparation of a compound of formula (I) in which R1 is C1-6 alkyl; R2 and R3 are independently hydrogen, halogen, trifluoromethyl or C1-6 alkoxy; R4 is C1-6 alkyl; R5 is hydrogen or C1-6 alkyl; and R6 is nitro or amino which comprises reacting a compound of formula (II) in which R1, R4 and R5 are as defined in formula (I) and X is a leading group with a compound of formula (III).(FR) Cette invention concerne de nouveaux produits intermédiaires et des procédés de préparation de composés de quinoline utiles en qualité de médicaments anti-paludiques, ainsi que de nouveaux produits intermédiaires utilisés dans ce procédé. Cette invention concerne un procédé de préparation d'un composé de formule (I) où R1 représente alkyle C1-6; R2 et R3 représentent indépendamment hydrogène, halogène, trifluorométhyle ou alcoxy C1-6; R4 représente alkyle C1-6; R5 représente hydrogène ou alkyle C1-6; et R6 représente nitro ou amino. Ce procédé consiste à faire réagir un composé de formule (II) où R1, R4 et R5 sont tels que définis dans la formule (I) et X est un groupe partant, avec un composé de formule (III).

  本发明涉及新型中间体和制备喹啉化合物的过程，其可用作抗疟药物，并涉及在该过程中有用的新型中间体。一种制备式（I）化合物的过程，其中R1为C1-6烷基；R2和R3分别为氢，卤素，三氟甲基或C1-6烷氧基；R4为C1-6烷基；R5为氢或C1-6烷基；R6为硝基或氨基，包括将式（II）化合物与式（III）化合物反应，其中R1，R4和R5在式（I）中定义，X为离去基团。
• WO2008/43726
  申请人：——

  公开号：——

  公开（公告）日：——
• PROCESS FOR THE PREPARATION OF ANTI-MALARIAL DRUGS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0871616A1

  公开（公告）日：1998-10-21
• SITAMAQUINE TOSYLATE FOR THE TREATMENT OF LEISHMANIASIS
  申请人：Glaxo Group Limited

  公开号：EP2081906A1

  公开（公告）日：2009-07-29