N2-(7-chloroquinolin-4-yl)-propane-1,2-diamine | 849179-93-7

• 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: N2-(7-chloroquinolin-4-yl)-propane-1,2-diamine
• 英文别名: N-(1-aminopropan-2-yl)-7-chloroquinolin-4-amine；2-N-(7-chloroquinolin-4-yl)propane-1,2-diamine
• CAS: 849179-93-7
• 化学式: C₁₂H₁₄ClN₃
• 分子量: 235.716
• InChiKey: DVZLCKWGOXAODS-UHFFFAOYSA-N

物化性质

• 熔点：
  126-127 °C
• 沸点：
  416.1±40.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N2-(7-chloroquinolin-4-yl)-propane-1,2-diamine 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 7.0h， 生成 N-[2-(7-chloroquinolin-4-ylamino)propyl]guanidine hydrochloride
  参考文献：
  名称：

  Design and synthesis of new antimalarial agents from 4-aminoquinoline

  摘要：

  This study describes the synthesis of new 4-aminoquinoline derivatives and evaluation of their activity against a chloroquine sensitive strain of P. falciparum in vitro and chloroquine resistant N-67 strain of P. yoelii in vivo. All the analogues were found to form strong complex with hematin and inhibit the P-hematin formation in vitro. These results suggest that these compounds act on heme polymerization target. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.051
• 作为产物：
  描述：

  7-氯-4-羟基喹啉 在 三氯氧磷 作用下， 反应 4.0h， 生成 N2-(7-chloroquinolin-4-yl)-propane-1,2-diamine
  参考文献：
  名称：

  抗疟药：合成4-氨基喹啉类药物，可在疟疾寄生虫中规避耐药性†

  摘要：

  此处描述的策略已允许合成一系列4-氨基喹啉抗疟药。对先前合成方法的实质性改进包括用纯胺而不是苯酚进行亲核取代，区域选择性还原烷基化以将二氨基烷烃侧链上的末端伯胺（12a-20a）转化为二乙氨基，以及通过使用碱性氧化铝的柱色谱法进行纯化。用硼氘化钠（与硼氢化钠相比）进行区域选择性还原烷基化后获得的1 H nmr光谱表明，该还原烷基化是通过形成并随后原位还原相应的二酰胺而进行的。

  DOI：

  10.1002/jhet.5570340149

文献信息

• Synthesis, antimalarial activity evaluation and docking studies of some novel tetraoxaquines
  作者：Mukesh Kumar Kumawat、Pratap Parida、Dipak Chetia

  DOI：10.1007/s00044-016-1644-5

  日期：2016.9

  designed via molecular docking analysis against Falcipain-2. Among the studied compounds, 11 top scoring analogues showing low binding energy were further selected for synthesis and evaluated for their in vitro antimalarial activity. In inhibitory assay, five compounds showed significant activity against chloroquine-resistant strain of P. falciparum-RKL-9 with IC50 values of 3.906, 3.942, 4.272, 3.906

  通过对Falcipain-2的分子对接分析，设计了1,2,4,5-四恶烷和4-氨基喹啉的分子杂合物四氧杂喹。在研究的化合物中，还进一步选择了11个具有较低结合能的得分最高的类似物进行合成，并对其体外抗疟活性进行了评估。在抑制分析中，五种化合物显示出对恶性疟原虫-RKL-9的耐氯喹菌株具有显着活性，IC 50值为3.906、3.942、4.272、3.906、4.814 µg / ml。
• 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.
• 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure–activity relationship and mode of action studies
  作者：Kamaljit Singh、Hardeep Kaur、Kelly Chibale、Jan Balzarini、Susan Little、Prasad V. Bharatam

  DOI：10.1016/j.ejmech.2012.03.007

  日期：2012.6

  2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC50 (3.6 nM) value (56-fold less than CQ) against CQ(R) strain. Structure activity profile and binding with heme, mu-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Antimalarials: Synthesis of 4-aminoquinolines that circumvent drug resistance in malaria parasites
  作者：Dibyendu De、Larry D. Byers、Donald J. Krogstad

  DOI：10.1002/jhet.5570340149

  日期：1997.1

  substitution with neat amine rather than in phenol, regioselective reductive alkylation to convert the terminal primary amine (12a–20a) on the diaminoalkane side chain to a diethylamino group, and purification by column chromatography with basic alumina. The 1H nmr spectra obtained after regioselective reductive alkylation with sodium borodeuteride (in comparison with sodium borohydride) demonstrated that

  此处描述的策略已允许合成一系列4-氨基喹啉抗疟药。对先前合成方法的实质性改进包括用纯胺而不是苯酚进行亲核取代，区域选择性还原烷基化以将二氨基烷烃侧链上的末端伯胺（12a-20a）转化为二乙氨基，以及通过使用碱性氧化铝的柱色谱法进行纯化。用硼氘化钠（与硼氢化钠相比）进行区域选择性还原烷基化后获得的1 H nmr光谱表明，该还原烷基化是通过形成并随后原位还原相应的二酰胺而进行的。
• Design and synthesis of new antimalarial agents from 4-aminoquinoline
  作者：V. Raja Solomon、Sunil K. Puri、Kumkum Srivastava、S.B. Katti

  DOI：10.1016/j.bmc.2004.12.051

  日期：2005.3

  This study describes the synthesis of new 4-aminoquinoline derivatives and evaluation of their activity against a chloroquine sensitive strain of P. falciparum in vitro and chloroquine resistant N-67 strain of P. yoelii in vivo. All the analogues were found to form strong complex with hematin and inhibit the P-hematin formation in vitro. These results suggest that these compounds act on heme polymerization target. (c) 2005 Elsevier Ltd. All rights reserved.