3-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-4-(5-chloro-2-hydroxy-phenyl)-6-trifluoromethyl-1H-quinolin-2-one | 863225-72-3

• 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: 3-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-4-(5-chloro-2-hydroxy-phenyl)-6-trifluoromethyl-1H-quinolin-2-one
• CAS: 863225-72-3
• 化学式: C₃₄H₃₁ClF₃NO₃Si
• 分子量: 622.159
• InChiKey: YVFGUZUDRKJSAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.69
• 重原子数：
  43.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  62.32
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-4-(5-chloro-2-hydroxy-phenyl)-6-trifluoromethyl-1H-quinolin-2-one 在 Pt on sulfided carbon lithium hydroxide 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 邻二氯苯 、 丙酮 为溶剂， 反应 102.0h， 生成
  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：

  叔丁基二苯基氯硅烷 、 BMS-223131 在 咪唑 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 3.0h， 以81%的产率得到3-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-4-(5-chloro-2-hydroxy-phenyl)-6-trifluoromethyl-1H-quinolin-2-one
  参考文献：
  名称：

  [EN] ATROPISOMERS OF 3-SUBSTITUTED-4-ARYLQUINOLIN-2-ONE DERIVATIVES
  [FR] ATROPISOMERES DE DERIVES DE 4-ARYLQUINOLIN-2-ONE SUBSTITUES EN POSITION 3

  摘要：

  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。

  公开号：

  WO2004058260A1

文献信息

• Analogs of a potent maxi-K potassium channel opener with an improved inhibitory profile toward cytochrome P450 isozymes
  作者：Vivekananda M. Vrudhula、Bireshwar Dasgupta、Christopher G. Boissard、Valentin K. Gribkoff、Kenneth S. Santone、Richard A. Dalterio、Nicholas J. Lodge、John E. Starrett

  DOI：10.1016/j.bmcl.2005.06.056

  日期：2005.10

  Quinolinone 1 is a potent maxi-K potassium channel opener. In an effort to design analogs of I with a better inhibitory profile toward the CYP2C9 isozyme, the two acidic sites were chemically modified independently to generate a number of analogs. These analogs were evaluated as maxi-K channel openers in vitro using Xenopus laevis oocytes expressing cloned hSlo maxi-K channels. Compounds 15, 17, and 19 showed potent activity as maxi-K channel openers and were further evaluated for inhibition of the activity of the CYP2C9 isozyme. Compounds 17 and 19 showed diminished inhibitory potency against 2C9 and also against a panel of other more common CYP isozymes. (c) 2005 Elsevier Ltd. All rights reserved.