2-(3-(2-(tert-butyldiphenylsilyloxy)ethyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydroquinolin-4-yl)-4-chlorophenyl acetate | 721918-21-4

• 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: 2-(3-(2-(tert-butyldiphenylsilyloxy)ethyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydroquinolin-4-yl)-4-chlorophenyl acetate
• 英文别名: acetic acid 2-{-[2-(tert-butyl-diphenyl-silanyloxy)-ethyl]-2-oxo-6-trifluoromethyl-1,2-dihydro-quinolin-4-yl}-4-chloro-phenyl ester；Acetic acid 2-{3-[2-(tert-butyl-diphenyl-silanyloxy)-ethyl]-2-oxo-6-trifluoromethyl-1,2-dihydro-quinolin-4-yl}-4-chloro-phenyl ester；[2-[3-[2-[tert-butyl(diphenyl)silyl]oxyethyl]-2-oxo-6-(trifluoromethyl)-1H-quinolin-4-yl]-4-chlorophenyl] acetate
• CAS: 721918-21-4
• 化学式: C₃₆H₃₃ClF₃NO₄Si
• 分子量: 664.196
• InChiKey: ACQONOAZJUNVBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.91
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3-(2-(tert-butyldiphenylsilyloxy)ethyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydroquinolin-4-yl)-4-chlorophenyl acetate 在 lithium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 邻二氯苯 、 丙酮 为溶剂， 反应 94.0h， 生成 3-(2-(tert-butyldiphenylsilyloxy)ethyl)-4-(5-chloro-2-hydroxy-3-(2-methylallyl)phenyl)-1-methyl-6-(trifluoromethyl)quinolin-2(1H)-one
  参考文献：
  名称：

  Atropisomeric 3-(β-hydroxyethyl)-4-arylquinolin-2-ones as Maxi-K Potassium Channel Openers

  摘要：

  The synthesis of a series of 3-beta-hydroxyethyl-4-arylquinolin-2-ones is described. These compounds contain hydrophilic and hydrophobic substituents ortho to the phenolic OH in the C ring of the quinolinone. Electrophysiological evaluation of the panel of compounds revealed that 11 and 16 with an unbranched ortho substituent retain activity as maxi-K ion channel openers. Members of this series of compounds can exist as stable atropisomers. Calculated estimates of the energy barrier for rotation around the aryl-aryl single bond in 3 is 31 kcal/mol. The atropisomers of (+/-)-3, (+/-)-4, and (+/-)-11 were separated by chiral HPLC and tested for their effect on maxi-K mediated outward current in hSlo injected X. laevis oocytes. The (-) isomer in each case was found to be more active than the corresponding (+) isomer, suggesting that the ion channel exhibits stereoselective activation. X-ray crystallographic structures of (+)-3 and (+)-11 were determined. Evaluation of the stability of (-)-3 at 80 degrees C in n-butanol indicated a 19.6% conversion to (+)-3 over 72 h. In human serum at 37 degrees C (-)-3 did not racemize over the course of the 30 h study.

  DOI：

  10.1021/jm061093j
• 作为产物：
  描述：

  BMS-223131 在 咪唑 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 2-(3-(2-(tert-butyldiphenylsilyloxy)ethyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydroquinolin-4-yl)-4-chlorophenyl acetate
  参考文献：
  名称：

  Atropisomeric 3-(β-hydroxyethyl)-4-arylquinolin-2-ones as Maxi-K Potassium Channel Openers

  摘要：

  The synthesis of a series of 3-beta-hydroxyethyl-4-arylquinolin-2-ones is described. These compounds contain hydrophilic and hydrophobic substituents ortho to the phenolic OH in the C ring of the quinolinone. Electrophysiological evaluation of the panel of compounds revealed that 11 and 16 with an unbranched ortho substituent retain activity as maxi-K ion channel openers. Members of this series of compounds can exist as stable atropisomers. Calculated estimates of the energy barrier for rotation around the aryl-aryl single bond in 3 is 31 kcal/mol. The atropisomers of (+/-)-3, (+/-)-4, and (+/-)-11 were separated by chiral HPLC and tested for their effect on maxi-K mediated outward current in hSlo injected X. laevis oocytes. The (-) isomer in each case was found to be more active than the corresponding (+) isomer, suggesting that the ion channel exhibits stereoselective activation. X-ray crystallographic structures of (+)-3 and (+)-11 were determined. Evaluation of the stability of (-)-3 at 80 degrees C in n-butanol indicated a 19.6% conversion to (+)-3 over 72 h. In human serum at 37 degrees C (-)-3 did not racemize over the course of the 30 h study.

  DOI：

  10.1021/jm061093j

文献信息

• [EN] ATROPISOMERS OF 3-SUBSTITUTED-4-ARYLQUINOLIN-2-ONE DERIVATIVES<br/>[FR] ATROPISOMERES DE DERIVES DE 4-ARYLQUINOLIN-2-ONE SUBSTITUES EN POSITION 3
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004058260A1

  公开（公告）日：2004-07-15

  Atropisomers of 3-substituted-4-arylquinolin-2-one derivatives having the general formula wherein R, R1, R2, R3, R4 and R5, are as defined herein, or a non-toxic pharmaceutically acceptable salt, solvate or prodrug thereof. The atropisomers can modulate the large conductance calcium-activated K+ channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels. In addition, the atropisomers can be stable, i.e., do not interconvert, for periods of up to one month, or more.

  具有下列一般式的3-取代-4-芳基喹啉-2-酮衍生物的异构体，其中R、R1、R2、R3、R4和R5如本文所定义，或其无毒药理学上可接受的盐、溶剂化合物或前药。这些异构体可以调节大电导钙激活K+通道，并可用于治疗对开放钾通道有反应的疾病。此外，这些异构体可以稳定，即不会在一个月或更长时间内互相转化。
• Atropisomers of 3-substituted-4-arylquinolin-2-one derivatives
  申请人：——

  公开号：US20040147749A1

  公开（公告）日：2004-07-29

  Atropisomers of 3-substituted-4-arylquinolin-2-one derivatives having the general formula 1 wherein R, R 1 , R 2 , R 3 , R 4 and R 5 , are as defined herein, or a non-toxic pharmaceutically acceptable salt, solvate or prodrug thereof. The atropisomers can modulate the large conductance calcium-activated K + channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels. In addition, the atropisomers can be stable, i.e., do not interconvert, for periods of up to one month, or more.

  具有一般式1的3-取代-4-芳基喹啉-2-酮衍生物的旋光异构体，其中R、R1、R2、R3、R4和R5如此处所定义，或其无毒药学上可接受的盐、溶剂化合物或前药。这些旋光异构体可以调节大电导钙激活K+通道，并可用于治疗对开放钾通道有反应的疾病。此外，这些旋光异构体可以稳定，即在长达一个月或更长时间内不会相互转化。