4-Bromo-6-chloro-2-methylquinoline | 1070879-50-3

• 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: 4-Bromo-6-chloro-2-methylquinoline
• CAS: 1070879-50-3
• 化学式: C₁₀H₇BrClN
• 分子量: 256.529
• InChiKey: BCPLJTKDWGUNKP-UHFFFAOYSA-N

物化性质

• 沸点：
  334.9±37.0 °C(Predicted)
• 密度：
  1.591±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-Bromo-6-chloro-2-methylquinoline 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 6-氯-2-甲基喹啉
  参考文献：
  名称：

  设计，合成和生物评价2-取代喹啉作为潜在的抗疟药

  摘要：

  为了确定潜在的候选药物治疗内脏利什曼病，合成了2-取代的喹啉化合物的类似物库。测试了这些分子对利什曼原虫的体外和体内生物活性。这些化合物的代谢稳定性也通过引入卤素取代基得到了改善。化合物（26g），被发现是最活跃的；IC 50值为0.2μM，选择性> 180倍。（26g）的盐酸盐在L. donovani中50 mg / kg×5天（每天两次，口服）剂量下显示84.26±4.44％的抑制作用/仓鼠模型。功效与观察到的PK数据高度相关，这表明该化合物分布均匀。

  DOI：

  10.1016/j.ejmech.2013.08.028
• 作为产物：
  描述：

  6-氯-2-甲基-4-羟基喹啉 在 三溴化磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-Bromo-6-chloro-2-methylquinoline
  参考文献：
  名称：

  设计，合成和生物评价2-取代喹啉作为潜在的抗疟药

  摘要：

  为了确定潜在的候选药物治疗内脏利什曼病，合成了2-取代的喹啉化合物的类似物库。测试了这些分子对利什曼原虫的体外和体内生物活性。这些化合物的代谢稳定性也通过引入卤素取代基得到了改善。化合物（26g），被发现是最活跃的；IC 50值为0.2μM，选择性> 180倍。（26g）的盐酸盐在L. donovani中50 mg / kg×5天（每天两次，口服）剂量下显示84.26±4.44％的抑制作用/仓鼠模型。功效与观察到的PK数据高度相关，这表明该化合物分布均匀。

  DOI：

  10.1016/j.ejmech.2013.08.028

文献信息

• Design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents
  作者：Vadiraj S. Gopinath、Jakir Pinjari、Ravindra T. Dere、Aditya Verma、Preeti Vishwakarma、Rahul Shivahare、Manjunath Moger、Palusa Sanath Kumar Goud、Vikram Ramanathan、Prosenjit Bose、M.V.S. Rao、Suman Gupta、Sunil K. Puri、Delphine Launay、Denis Martin

  DOI：10.1016/j.ejmech.2013.08.028

  日期：2013.11

  An analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. These molecules were tested for their in vitro and in vivo biological activity against Leishmania donovani. Metabolic stability of these compounds was also improved through the introduction of halogen substituents. Compound (26g), found to be

  为了确定潜在的候选药物治疗内脏利什曼病，合成了2-取代的喹啉化合物的类似物库。测试了这些分子对利什曼原虫的体外和体内生物活性。这些化合物的代谢稳定性也通过引入卤素取代基得到了改善。化合物（26g），被发现是最活跃的；IC 50值为0.2μM，选择性> 180倍。（26g）的盐酸盐在L. donovani中50 mg / kg×5天（每天两次，口服）剂量下显示84.26±4.44％的抑制作用/仓鼠模型。功效与观察到的PK数据高度相关，这表明该化合物分布均匀。
• Design, synthesis, ADME characterization and antileishmanial evaluation of novel substituted quinoline analogs
  作者：Vadiraj S. Gopinath、Mukkavilli Rao、Rahul Shivahare、Preeti Vishwakarma、Sweta Ghose、Ashok Pradhan、Ramamohan Hindupur、Koushik Das Sarma、Suman Gupta、Sunil K. Puri、Delphine Launay、Denis Martin

  DOI：10.1016/j.bmcl.2014.03.065

  日期：2014.5

  In vitro ADME characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. Compound 1 was highly permeable in intestinal PAMPA model (31 x 10(-6) cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. Compound 1 was found to have no CYP450 liability with CYP2C9, 2C19, 2D6 and 3A4. It showed inhibition with CYP1A2 with an IC50 value of 0.50 mu M. Analogs of 1 were synthesized and subsequently characterized for in vitro activity against the intracellular form of Leishmania donovani. Resulting quinolines were found to have similar efficacy as 1 against the parasite. Compounds 8b and 8f were found to be the most active with IC50 values of 0.84 mu M and 0.17 mu M, respectively compared to 0.22 mu M for compound 1. Of all the analogs tested, 8d was stable in hamster, mouse and human liver microsomes but lost the efficacy with an IC50 of 6.42 mu M. Based on the in vitro efficacy and DMPK profile, compounds 8b and 8f seem the best candidates to be screened in further assays. (C) 2014 Elsevier Ltd. All rights reserved.