N-(7-chloro-quinolin-4-yl)-benzene-1,3-diamine | 1019356-15-0

• 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: N-(7-chloro-quinolin-4-yl)-benzene-1,3-diamine
• 英文别名: 3-N-(7-chloroquinolin-4-yl)benzene-1,3-diamine
• CAS: 1019356-15-0
• 化学式: C₁₅H₁₂ClN₃
• 分子量: 269.733
• InChiKey: RBHKQAPHBJZVIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  N-(7-chloro-quinolin-4-yl)-benzene-1,3-diamine 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 N-[3-(7-chloro-quinolin-4-ylamino)-phenyl]-N'-(3-morpholin-4-yl-propyl)-N''-p-tolyl-[1,3,5]triazine-2,4,6-triamine
  参考文献：
  名称：

  4-Anilinoquinoline triazines: A novel class of hybrid antimalarial agents

  摘要：

  A novel class of hybrid 4-anilinoquinoline triazines have been synthesized and evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of P. falciparum as well as for their cytotoxicity toward VERO cell line. Five compounds (19, 20, 23, 41 and 45) exhibited the antimalarial potency superior to CQ. Compounds 14 and 16 were found to be orally active at a dose of 100 mg/kg x 4 days against CQ-resistant strain of P. yoelii. Inhibition of (beta-hematin formation assay and molecular docking study has been conducted in order to gain insight into the mechanism of action of proposed targets for the 4-anilinoquinoline and triazine moiety of the hybrid compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.12.003
• 作为产物：
  描述：

  4,7-二氯喹啉 、 间苯二胺 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以93%的产率得到N-(7-chloro-quinolin-4-yl)-benzene-1,3-diamine
  参考文献：
  名称：

  合成新型4-氨基喹啉和喹啉-啶杂化物作为抗疟剂

  摘要：

  尽管在大多数流行地区对CQ和其他4-氨基喹啉药物均产生了抗药性，但研究结果提供了相当大的支持，即仍有巨大的潜力发现价格合理，安全且有效的新型4-氨基喹啉抗疟药。在本研究中，合成了新的侧链修饰的4-氨基喹啉衍生物和喹啉-r啶杂化物，并在体外针对恶性疟原虫的NF 54菌株进行了评估。在评估的化合物中，化合物17（MIC = 0.125μg/ mL）与标准药物CQ（MIC = 0.125μg/ mL）等价，化合物21（MIC = 0.031μg/ mL）的效力是CQ的四倍。化合物17显示通过腹膜内途径对剂量为50 mg / kg和25 mg / kg的CQ耐药约氏疟原虫N-67株感染的所有治疗过的瑞士小鼠进行了4天的治愈反应，并发现在该剂量下具有口服活性100 mg / kg的剂量持续4天。化合物17的有希望的抗疟药效力突出了探索针对新型抗疟药的特权4-氨基喹啉类的重要性。

  DOI：

  10.1016/j.bmcl.2010.09.107

文献信息

• Synthesis of new 4-aminoquinolines and quinoline–acridine hybrids as antimalarial agents
  作者：Ashok Kumar、Kumkum Srivastava、S. Raja Kumar、S.K. Puri、Prem M.S. Chauhan

  DOI：10.1016/j.bmcl.2010.09.107

  日期：2010.12

  4-aminoquinoline drugs in most of the endemic regions, research findings provide considerable support that there is still significant potential to discover new affordable, safe, and efficacious 4-aminoquinoline antimalarials. In present study, new side chain modified 4-aminoquinoline derivatives and quinoline–acridine hybrids were synthesized and evaluated in vitro against NF 54 strain of Plasmodium

  尽管在大多数流行地区对CQ和其他4-氨基喹啉药物均产生了抗药性，但研究结果提供了相当大的支持，即仍有巨大的潜力发现价格合理，安全且有效的新型4-氨基喹啉抗疟药。在本研究中，合成了新的侧链修饰的4-氨基喹啉衍生物和喹啉-r啶杂化物，并在体外针对恶性疟原虫的NF 54菌株进行了评估。在评估的化合物中，化合物17（MIC = 0.125μg/ mL）与标准药物CQ（MIC = 0.125μg/ mL）等价，化合物21（MIC = 0.031μg/ mL）的效力是CQ的四倍。化合物17显示通过腹膜内途径对剂量为50 mg / kg和25 mg / kg的CQ耐药约氏疟原虫N-67株感染的所有治疗过的瑞士小鼠进行了4天的治愈反应，并发现在该剂量下具有口服活性100 mg / kg的剂量持续4天。化合物17的有希望的抗疟药效力突出了探索针对新型抗疟药的特权4-氨基喹啉类的重要性。
• Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens
  作者：Neveen M. Saleh、Yasmine S. Moemen、Sara H. Mohamed、Ghady Fathy、Abdullah A. S. Ahmed、Ahmed A. Al-Ghamdi、Sami Ullah、Ibrahim El-Tantawy El Sayed

  DOI：10.3390/antibiotics11010053

  日期：——

  DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates (1a–e and 2a–e) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound (2a) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC50 of 12.03 µM. In addition, a docking study was performed with inhibitor (2a), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor (2a) to DNA gyrase is mediated and modulated by divalent Mg2+ at good binding energy (–9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.

  DNA酶旋转酶和拓扑异构酶IV已被证明是设计新型抗菌药物的验证目标。在本研究中，我们报告了之前合成的两系列环状二苯基膦酸酯（1a-e和2a-e）作为DNA酶旋转酶抑制剂的抗菌评估和分子对接研究。筛选合成的化合物在对带有DNA酶旋转酶QRDR区域突变（缺失和替换）的耐环丙沙星的大肠杆菌和肺炎克雷伯菌临床分离株的活性（抗菌和DNA酶旋转酶抑制）方面进行了评估。选择对耐环丙沙星革兰氏阴性临床分离株表现出最强活性的目标化合物（2a），对其在DNA酶旋转酶上的抑制活性进行筛选，其显示的IC50为12.03微摩尔。此外，对抑制剂（2a）进行了对接研究，以说明其在DNA酶旋转酶的活性位点中的结合方式，结果与观察到的抑制效力相容。此外，对接研究揭示了抑制剂（2a）与DNA酶旋转酶的结合是通过二价Mg2+介导和调节的，其结合能为良好结合能（-9.08千卡/摩尔）。此外，结构-活性关系（SAR）表明，在环状二苯基膦酸酯基底中结合肼基团的组合导致了一种优化的分子，通过其在体外对酶催化DNA超螺旋化活性的可检测效应抑制了细菌DNA酶旋转酶。
• 4-Anilinoquinoline triazines: A novel class of hybrid antimalarial agents
  作者：Ashok Kumar、Kumkum Srivastava、S. Raja Kumar、M.I. Siddiqi、Sunil K. Puri、Jitendra K. Sexana、Prem M.S. Chauhan

  DOI：10.1016/j.ejmech.2010.12.003

  日期：2011.2

  A novel class of hybrid 4-anilinoquinoline triazines have been synthesized and evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of P. falciparum as well as for their cytotoxicity toward VERO cell line. Five compounds (19, 20, 23, 41 and 45) exhibited the antimalarial potency superior to CQ. Compounds 14 and 16 were found to be orally active at a dose of 100 mg/kg x 4 days against CQ-resistant strain of P. yoelii. Inhibition of (beta-hematin formation assay and molecular docking study has been conducted in order to gain insight into the mechanism of action of proposed targets for the 4-anilinoquinoline and triazine moiety of the hybrid compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.