[5-[Tert-butyl(dimethyl)silyl]oxy-6-methoxyquinolin-2-yl]-(3,4,5-trimethoxyphenyl)methanone | 1350735-51-1

• 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-[Tert-butyl(dimethyl)silyl]oxy-6-methoxyquinolin-2-yl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1350735-51-1
• 化学式: C₂₆H₃₃NO₆Si
• 分子量: 483.637
• InChiKey: YWOWHGRPIDVXPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [5-[Tert-butyl(dimethyl)silyl]oxy-6-methoxyquinolin-2-yl]-(3,4,5-trimethoxyphenyl)methanone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 5-hydroxy-6-methoxy-2-(3',4',5'-trimethoxybenzoyl)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
• 作为产物：
  描述：

  6-甲氧基-2-甲基喹啉 在 selenium(IV) oxide 、 N-溴代丁二酰亚胺(NBS) 、 重铬酸吡啶 、 四(三苯基膦)钯 、 三乙胺 、 N,N-二异丙基乙胺 、 频那醇硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 对二甲苯 、 乙腈 为溶剂， 反应 71.25h， 生成 [5-[Tert-butyl(dimethyl)silyl]oxy-6-methoxyquinolin-2-yl]-(3,4,5-trimethoxyphenyl)methanone
  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

• 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.