BMS-223131 | 722497-39-4

• 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: BMS-223131
• 英文别名: 4-(5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-6-(trifluoromethyl)-2(1H)-quinolinone；4-(5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-6-(trifluoromethyl)-1H-quinolin-2-one
• CAS: 722497-39-4
• 化学式: C₁₈H₁₃ClF₃NO₃
• 分子量: 383.754
• InChiKey: QESHSZWKJULSAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  BMS-223131 在 Pt on sulfided carbon 咪唑 、 lithium hydroxide 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 邻二氯苯 、 丙酮 为溶剂， 反应 105.0h， 生成 4-[5-Chloro-2-hydroxy-3-(2-methylpropyl)phenyl]-3-(2-hydroxyethyl)-1-methyl-6-(trifluoromethyl)quinolin-2-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：

  (2-氨基-5-三氟甲基-苯基)-(5-氯-2-甲氧基-苯基)-甲酮 在 吡啶 、 dimethyl sulfide borane 、 氢溴酸 、 吡啶盐酸盐 、 双(三甲基硅烷基)氨基钾 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 BMS-223131
  参考文献：
  名称：

  4-Aryl-3-(hydroxyalkyl)quinolin-2-ones:  Novel Maxi-K Channel Opening Relaxants of Corporal Smooth Muscle Targeted for Erectile Dysfunction

  摘要：

  Novel 4-aryl-3-(hydroxyalkyl)quinoline-2-one derivatives were prepared and evaluated as openers of the cloned maxi-K channel hSlo expressed in Xenopus laevis oocytes by utilizing electrophysiological methods. The effect of these maxi-K openers on corporal smooth muscle was studied in vitro using isolated rabbit corpus cavernosum. From this study, a potent maxi-K opener was identified as an effective relaxant of rabbit corporal smooth muscle and shown to be active in an in vivo animal model of male erectile function.

  DOI：

  10.1021/jm030005h

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。
• Preparation of 3-substituted-4-arylquinolin-2-one derivatives
  申请人：Bristol-Myers Squibb Company

  公开号：US06353119B1

  公开（公告）日：2002-03-05

  The present invention relates to a process for the preparation of 3-substituted-4-arylquinolin-2-one derivatives from a substituted coumarin and using a photochemical cyclization method on a dihydrofuran intermediate.

  本发明涉及一种从取代香豆素出发，利用二氢呋喃中间体的光化学环化方法制备3-取代-4-芳基喹啉-2-酮衍生物的工艺。
• [EN] 3-SUBSTITUTED-4-ARYLQUINOLIN-2-ONE DERIVATIVES AS POTASSIUM CHANNEL MODULATORS<br/>[FR] DERIVES 3-SUBSTITUES DE 4-ARYLQUINOLIN-2-ONE UTILISES COMME MODULATEURS DES CANAUX POTASSIQUES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2000034244A1

  公开（公告）日：2000-06-15

  The present invention provides novel 3-substituted-4-arylquinolin-2-one derivatives having general formula (I) wherein R, R?1, R2, R3, R4, R5, R6 and R7¿ are as defined herein, or a nontoxic pharmaceutically acceptable salt thereof which are modulators of 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.

  本发明提供了一种新型的3-取代-4-芳基喹啉-2-酮衍生物，其具有通式（I），其中R，R?1，R2，R3，R4，R5，R6和R7¿如本文所定义，或其无毒的药学上可接受的盐，它们是大电导钙激活K+通道的调节剂，并且在治疗对钾通道开放有反应的疾病方面很有用。
• 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。
• Selective removal of a benzyl protecting group in the presence of an aryl chloride under gaseous and transfer hydrogenolysis conditions
  作者：Jun Li、Steve Wang、Gerard A Crispino、Karen Tenhuisen、Ambarish Singh、John A Grosso

  DOI：10.1016/s0040-4039(03)00846-3

  日期：2003.5

  Selective removal of a benzyl protecting group in the presence of an aryl chloride using Pd/C under gaseous and transfer hydrogenolysis conditions is described. The addition of chloride salts to the debenzylation reaction provides excellent selectivity.

  描述了在气态和转移氢解条件下使用Pd / C在芳基氯存在下选择性除去苄基保护基的方法。在脱苄基反应中加入氯化物盐可提供出色的选择性。