5-amino-6-methoxy-2-(3',4',5'-trimethoxyphenylthio)quinoline | 1346169-90-1

• 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: 5-amino-6-methoxy-2-(3',4',5'-trimethoxyphenylthio)quinoline
• 英文别名: 6-Methoxy-2-(3,4,5-trimethoxyphenyl)sulfanylquinolin-5-amine
• CAS: 1346169-90-1
• 化学式: C₁₉H₂₀N₂O₄S
• 分子量: 372.445
• InChiKey: YUBJMFKNJPPSMX-UHFFFAOYSA-N

物化性质

• 沸点：
  581.6±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-甲氧基喹啉 在 硫酸 、 硝酸 、 铁粉 、 氯化铵 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 4.0h， 生成 5-amino-6-methoxy-2-(3',4',5'-trimethoxyphenylthio)quinoline
  参考文献：
  名称：

  5-Amino-2-aroylquinolines as Highly Potent Tubulin Polymerization Inhibitors. Part 2. The Impact of Bridging Groups at Position C-2

  摘要：

  A variety of studies on the modification of combretastatin A-4 triggered our interest in the impact of the linkers between the 3,4,5-trimethoxyphenyl ring and 5-amino-6-methoxyquinoline on biological activity. The replacement of the carbonyl group with bond, amine, ether, sulfide, and sulfone groups was evaluated in this study. The results showed that compounds 14 and 15 containing sulfide and sulfone groups between the 3,4,5-trimethoxyphenyl ring (A-ring) and 5-amino-6-methoxyquinoline exhibited substantial antiproliferative activity against KB, HT29, and MKN45 cells with mean IC50 values of 42 and 12 nM, respectively. 15 inhibited the tubulin polymerization with an IC50 value of 2.0 mu M, similar to that with CA4. The continued work on the C-5 substituents of 3',4',5'-trimethoxybenzoyl-6-methoxyquinoline derivatives demonstrated that compound 7 possessing OH at C-5 exhibited excellent antiproliferative activity with mean IC50 values of 3.4 nM and microtubule destabilizing potency with an IC50 of 1.5 mu M, comparable to that of CA4 (IC50 = 1.9 mu M). It also exhibited substantial vascular disrupting effects. Compounds 7 and 15 exhibited significant efficacy against MDR/MRP-related drug-resistant cell lines (KB-vin10, KB-S15, and KB-7D) with mean IC50 values of 6.7 and 2.6 nM, respectively.

  DOI：

  10.1021/jm201031f

文献信息

• AROYLQUINOLINE COMPOUNDS
  申请人：Liou Jing-Ping

  公开号：US20110275643A1

  公开（公告）日：2011-11-10

  A serious of nitro heterocyclic derivatives including a structure of formula (I) are provided. In formula (I), P, Q and R1 to R8 are defined in the specification. The derivatives disclosed in the present invention are characterized in inhibiting tubulin polymerization, and treating cancers and other tubulin polymerization-related disorders with a suitable pharmaceutical acceptable carrier.

  提供了一系列含有结构式（I）的硝基杂环衍生物。在结构式（I）中，P、Q和R1至R8在说明书中有定义。本发明揭示的衍生物具有抑制微管聚合的特性，并可使用合适的药用载体治疗癌症和其他与微管聚合有关的疾病。
• 5-Amino-2-aroylquinolines as Highly Potent Tubulin Polymerization Inhibitors. Part 2. The Impact of Bridging Groups at Position C-2
  作者：Hsueh-Yun Lee、Jang-Yang Chang、Chih-Ying Nien、Ching-Chuan Kuo、Kuang-Hsing Shih、Chun-Hsein Wu、Chi-Yen Chang、Wen-Yang Lai、Jing-Ping Liou

  DOI：10.1021/jm201031f

  日期：2011.12.22

  A variety of studies on the modification of combretastatin A-4 triggered our interest in the impact of the linkers between the 3,4,5-trimethoxyphenyl ring and 5-amino-6-methoxyquinoline on biological activity. The replacement of the carbonyl group with bond, amine, ether, sulfide, and sulfone groups was evaluated in this study. The results showed that compounds 14 and 15 containing sulfide and sulfone groups between the 3,4,5-trimethoxyphenyl ring (A-ring) and 5-amino-6-methoxyquinoline exhibited substantial antiproliferative activity against KB, HT29, and MKN45 cells with mean IC50 values of 42 and 12 nM, respectively. 15 inhibited the tubulin polymerization with an IC50 value of 2.0 mu M, similar to that with CA4. The continued work on the C-5 substituents of 3',4',5'-trimethoxybenzoyl-6-methoxyquinoline derivatives demonstrated that compound 7 possessing OH at C-5 exhibited excellent antiproliferative activity with mean IC50 values of 3.4 nM and microtubule destabilizing potency with an IC50 of 1.5 mu M, comparable to that of CA4 (IC50 = 1.9 mu M). It also exhibited substantial vascular disrupting effects. Compounds 7 and 15 exhibited significant efficacy against MDR/MRP-related drug-resistant cell lines (KB-vin10, KB-S15, and KB-7D) with mean IC50 values of 6.7 and 2.6 nM, respectively.