2-[(7-chloroquinolin-4-yl)amino]propanol

• 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: 2-[(7-chloroquinolin-4-yl)amino]propanol
• 英文别名: 7-chloro-4-[(2-hydroxy-1-methylethyl)amino]quinoline；7-chloro-N-(2-hydroxy-1-methylethyl)-4-quinolinamine；(S)-2-amino-N-(7-chloro-quinolin-4-yl)-1-propanol；2-[(7-chloroquinolin-4-yl)amino]propan-1-ol
• 化学式: C₁₂H₁₃ClN₂O
• mdl: MFCD12184871
• 分子量: 236.701
• InChiKey: GJKZKBZGAVBCGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(7-chloroquinolin-4-yl)amino]propanol 在 硫酸 、 水 、 氢溴酸 作用下， 反应 3.5h， 以53%的产率得到4-[(2-bromo-1-methylethyl)amino]-7-chloroquinoline
  参考文献：
  名称：

  带有大体积基本侧链的新型氯喹类似物的合成和抗血浆活性

  摘要：

  氯喹通常用于治疗和预防疟疾，但是造成疟疾相关死亡的主要物种恶性疟原虫已对该药产生耐药性。二十七种新颖的氯喹（CQ）类似物，特征在于侧链以庞大的基本头基终止，即八氢-2 H-喹啉和1,2,3,4,5,6-六氢-1,5-甲基合成了8 H-吡啶并[1,2- a ] [1,5]重氮星-8-one，并测试了其对P的D-10（CQ敏感）和W-2（CQ抗性）菌株的活性。恶性疟原虫。使用纳摩尔或亚摩尔浓度的IC 50，发现大多数化合物对两种菌株均具有活性价值观。发现有11种化合物对W-2菌株的效力比CQ高2.7至13.4倍；其中，四种半胱氨酸衍生物似乎特别受关注，因为它们结合了对两种人类细胞系（HMEC-1和HepG2）的高效力和低细胞毒性，并且易于合成。用硫桥取代4-NH基团可保持较低的抗血浆活性，但提高了抗性因子。这些化合物作为抗击疟疾的潜在药物值得进一步研究。

  DOI：

  10.1002/cmdc.201500195
• 作为产物：
  描述：

  DL-氨基丙醇 、 4,7-二氯喹啉 反应 3.0h， 以82%的产率得到2-[(7-chloroquinolin-4-yl)amino]propanol
  参考文献：
  名称：

  带有大体积基本侧链的新型氯喹类似物的合成和抗血浆活性

  摘要：

  氯喹通常用于治疗和预防疟疾，但是造成疟疾相关死亡的主要物种恶性疟原虫已对该药产生耐药性。二十七种新颖的氯喹（CQ）类似物，特征在于侧链以庞大的基本头基终止，即八氢-2 H-喹啉和1,2,3,4,5,6-六氢-1,5-甲基合成了8 H-吡啶并[1,2- a ] [1,5]重氮星-8-one，并测试了其对P的D-10（CQ敏感）和W-2（CQ抗性）菌株的活性。恶性疟原虫。使用纳摩尔或亚摩尔浓度的IC 50，发现大多数化合物对两种菌株均具有活性价值观。发现有11种化合物对W-2菌株的效力比CQ高2.7至13.4倍；其中，四种半胱氨酸衍生物似乎特别受关注，因为它们结合了对两种人类细胞系（HMEC-1和HepG2）的高效力和低细胞毒性，并且易于合成。用硫桥取代4-NH基团可保持较低的抗血浆活性，但提高了抗性因子。这些化合物作为抗击疟疾的潜在药物值得进一步研究。

  DOI：

  10.1002/cmdc.201500195

文献信息

• Dihydro-1,4-oxazino(2,3-C)quinolines
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US04743601A1

  公开（公告）日：1988-05-10

  There are disclosed novel compounds of the formula ##STR1## where X is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, nitro or trifluoromethyl; R.sub.1 is hydrogen or loweralkyl; R.sub.2 is hydrogen, loweralkyl, arylloweralkyl or --(CH.sub.2).sub.m R.sub.7 wherein m is 1, 2 or 3 and R.sub.7 is cyano or amino; R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R.sub.5 and R.sub.6 are independently hydrogen or loweralkyl, or R.sub.5 +R.sub.6 taken together with the carbon atom to which they are attached constitute a cyclobutane, cyclopentane, cyclohexane, cycloheptane, pyrrolidine, piperidine, morpholine or thiomorpholine ring, or R.sub.5 is hydrogen and R.sub.6 is aryl or --CH.sub.2 OR.sub.8 wherein R.sub.8 is hydrogen, loweralkyl or loweralkylcarbonyl, which are useful for enhancing memory.

  揭示了一种新型化合物，其化学式为##STR1## 其中X是氢、较低烷基、较低烷氧基、羟基、卤素、硝基或三氟甲基；R.sub.1是氢或较低烷基；R.sub.2是氢、较低烷基、芳基较低烷基或--(CH.sub.2).sub.m R.sub.7，其中m为1、2或3，R.sub.7是氰基或氨基；R.sub.3和R.sub.4独立地是氢或较低烷基；R.sub.5和R.sub.6独立地是氢或较低烷基，或R.sub.5 +R.sub.6与它们连接的碳原子一起构成环丁烷、环戊烷、环己烷、环庚烷、吡咯烷、哌啶、吗啉或硫代吗啉环，或者R.sub.5是氢，R.sub.6是芳基或--CH.sub.2 OR.sub.8，其中R.sub.8是氢、较低烷基或较低烷基羰基，这些化合物有助于增强记忆。
• Dihydro-4(hydroxyalkyeneamino)quinolines
  申请人：Hoechst-Roussel Pharmaceuticals Incorporated

  公开号：US05182275A1

  公开（公告）日：1993-01-26

  There are disclosed novel compounds of the formula ##STR1## where X is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, nitro or trifluoromethyl; R.sub.1 is hydrogen or loweralkyl; R.sub.2 is hydrogen, loweralkyl, arylloweralkyl or --(CH.sub.2).sub.m R.sub.7 wherein m is 1, 2 or 3 and R.sub.7 is cyano or amino; R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R.sub.5 and R.sub.6 are independently hydrogen or loweralkyl, or R.sub.5 +R.sub.6 taken together with the carbon atom to which they are attached constitute a cyclobutane, cyclopentane, cyclohexane, cycloheptane, pyrrolidine, piperidine, morpholine or thiomorpholine ring, or R.sub.5 is hydrogen and R.sub.6 is aryl or --CH.sub.2 OR.sub.8 wherein R.sub.8 is hydrogen, loweralkyl or loweralkylcarbonyl, which are useful for enhancing memory.

  本发明公开了一种新型化合物的结构式，其中X为氢、低烷基、低烷氧基、羟基、卤素、硝基或三氟甲基；R1为氢或低烷基；R2为氢、低烷基、芳基低烷基或-(CH2)mR7，其中m为1、2或3，R7为氰基或氨基；R3和R4独立地为氢或低烷基；R5和R6独立地为氢或低烷基，或R5 + R6与它们附着的碳原子一起构成环丁烷、环戊烷、环己烷、环庚烷、吡咯烷、哌嗪烷、吗啉或硫代吗啉环，或R5为氢且R6为芳基或-CH2OR8，其中R8为氢、低烷基或低烷基羰基，这些化合物对增强记忆有用。
• Hydroxyquinoline amines, and method of enhancing memory in mammals
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US04942168A1

  公开（公告）日：1990-07-17

  There are disclosed novel compounds of the formula ##STR1## where X is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, nitro or trifluoromethyl; R.sub.1 is hydrogen or loweralkyl; R.sub.2 is hydrogen, loweralkyl, arylloweralkyl or --(CH.sub.2).sub.m R.sub.7 wherein m is 1, 2 or 3 and R.sub.7 is cyano or amino; R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R.sub.5 and R.sub.6 are independently hydrogen or loweralkyl, or R.sub.5 +R.sub.6 taken together with the carbon atom to which they are attached constitute a cyclobutane, cyclopentane, cyclohexane, cycloheptane, pyrrolidine, piperidine, morpholine or thiomorpholine ring, or R.sub.5 is hydrogen and R.sub.6 is aryl or --CH.sub.2 OR.sub.8 wherein R.sub.8 is hydrogen, loweralkyl or loweralkylcarbonyl, which are useful for enhancing memory.

  本发明公开了一种新型化合物，其化学式为##STR1##其中X为氢、低碳基、低氧基、羟基、卤素、硝基或三氟甲基；R.sub.1为氢或低碳基；R.sub.2为氢、低碳基、芳基低碳基或--(CH.sub.2).sub.m R.sub.7，其中m为1、2或3，R.sub.7为氰基或氨基；R.sub.3和R.sub.4分别为氢或低碳基；R.sub.5和R.sub.6分别为氢或低碳基，或R.sub.5+R.sub.6与它们附着的碳原子一起构成环丁烷、环戊烷、环己烷、环庚烷、吡咯烷、哌嗪烷、吗啉或硫代吗啉环，或R.sub.5为氢，R.sub.6为芳基或--CH.sub.2 OR.sub.8，其中R.sub.8为氢、低碳基或低碳基酰基，其对增强记忆有用。
• Dihydro-1,4-oxazino(2,3-c)quinolines, a process and intermediates for the preparation thereof and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0299345A2

  公开（公告）日：1989-01-18

  The present application relates to compounds of the formula I where X is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, nitro or trifluoromethyl; R₁ is hydrogen or loweralkyl; R₂ is hydrogen, loweralkyl, arylloweralkyl or -(CH₂)mR₇ wherein m is 1, 2 or 3 and R₇ is cyano or amino; R₃ and R₄ are independently hydrogen or loweralkyl; R₅ and R₆ are independently hydrogen or loweralkyl, or R₅+R₆ taken together with the carbon atom to which they are attached constitute a cyclobutane, cyclopentane, cyclohexane, cycloheptane, pyrrolidine, piperidine, morpholine or thiomorpholine ring, or R₅ is hydrogen and R₆ is aryl or -CH₂OR₈ wherein R₈ is hydrogen, loweralkyl or loweralkylcarbonyl, which are useful for enhancing memory. and a process for their preparation. The invention relates also to compounds of the formula II where X, R₁ and R₃ through R₆ are as defined earlier and R₉ is hydrogen or bromine (with the proviso that when R₁=R₃=R₄=R₅=R₆=R₉=H, X is not 7-chloro) which are also useful for enhancing memory and for preparing compounds of formula I.

  本申请涉及式 I 的化合物 其中 X 是氢、低级烷基、低级烷氧基、羟基、卤素、硝基或三氟甲基；R₁ 是氢或低级烷基；R₂ 是氢、低级烷基、芳基低级烷基或-(CH₂)mR₇，其中 m 是 1、2 或 3，R₇ 是氰基或氨基；R₃ 和 R₄ 独立地是氢或低级烷基；R₅ 和 R₆ 独立地为氢或低级烷基，或 R₅+R₆ 与它们所连接的碳原子一起构成环丁烷、环戊烷、环己烷、环庚烷吡咯烷、哌啶、吗啉或硫代吗啉环，或 R₅ 为氢且 R₆ 为芳基或 -CH₂OR₈ 其中 R₈ 为氢、低级烷基或低级烷基羰基。及其制备工艺。 本发明还涉及式 II 的化合物 其中 X、R₁ 和 R₃ 至 R₆ 如前定义，R₉ 是氢或溴 (但当 R₁=R₃=R₄=R₅=R₆=R₉=H 时，X 不是 7-氯)，这些化合物也有助于增强记忆力和制备式 I 的化合物。
• Synthesis, characterization and antimalarial activity of quinoline–pyrimidine hybrids
  作者：Stefan I. Pretorius、Wilma J. Breytenbach、Carmen de Kock、Peter J. Smith、David D. N’Da

  DOI：10.1016/j.bmc.2012.10.019

  日期：2013.1

  The aim of this study was to synthesize a series of quinoline-pyrimidine hybrids and to evaluate their in vitro antimalarial activity as well as cytotoxicity. The hybrids were brought about in a two-step nucleophilic substitution process involving quinoline and pyrimidine moieties. They were screened alongside chloroquine (CQ), pyrimethamine (PM) and fixed combinations thereof against the D10 and Dd2 strains of Plasmodium falciparum. The cytotoxicity was determined against the mammalian Chinese Hamster Ovarian cell line. The compounds were all active against both strains. However, hybrid (21) featuring piperazine linker stood as the most active of all. It was found as potent as CQ and PM against the D10 strain, and possessed a moderately superior potency over CQ against the Dd2 strain (IC50: 0.157 vs 0.417 mu M, similar to threefold), and also displayed activity comparable to that of the equimolar fixed combination of CQ and PM against both strains. (C) 2012 Elsevier Ltd. All rights reserved.