3-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one hydrochloride | 415684-58-1

• 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: 3-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one hydrochloride
• 英文别名: 3-(5-{[4-(methanesulfonyl)-1-piperazinyl]methyl}-1H-indol-2-yl)-quinolin-2(1H)-one hydrochloride；3-[5-[(4-methylsulfonylpiperazin-1-yl)methyl]-1H-indol-2-yl]-1H-quinolin-2-one;hydrochloride
• CAS: 415684-58-1
• 化学式: C₂₃H₂₄N₄O₃S*ClH
• 分子量: 472.995
• InChiKey: UEQCBXMIAZDDGG-UHFFFAOYSA-N

物化性质

• 熔点：
  250 °C

计算性质

• 辛醇/水分配系数(LogP)：
  3.18
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  93.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯喹啉 在 palladium diacetate 、 四丙基高钌酸铵 2-双环己基膦-2',6'-二甲氧基联苯 、 盐酸 、 potassium phosphate 、 lithium aluminium tetrahydride 、 硼酸三异丙酯 、 4 A molecular sieve 、 三乙酰氧基硼氢化钠 、 N-甲基吗啉氧化物 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 54.5h， 生成 3-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one hydrochloride
  参考文献：
  名称：

  以Pd催化串联CN /铃木偶联为关键步骤的KDR激酶抑制剂的高效合成

  摘要：

  包含吲哚-2-基喹啉-2-酮结构的四个有效的KDR激酶抑制剂家族正在利用Pd催化的串联CN和C偶联序列。

  DOI：

  10.1021/jo062228w

文献信息

• Synthesis of Novel KDR Kinase Inhibitors through Catalytic Reductive Cyclization of <i>o</i>-Nitrobenzylcarbonyl Compounds
  作者：Audrey Wong、Jeffrey T. Kuethe、Ian W. Davies、David L. Hughes

  DOI：10.1021/jo048843m

  日期：2004.10.1

  through the Swern-type oxidation of readily accessible phenethanol analogues. Reductive cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H-indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase inhibitor 1 in quantitative yield. The examination of the reductive cyclization reaction and optimization of conditions is described.

  通过容易获得的苯乙醇类似物的Swern型氧化证明了邻硝基苄基羰基化合物的有效合成。使用催化阮内镍对邻硝基苄基羰基3进行还原环化，可得到1 H-吲哚-2-基-1 H-喹啉2，产率为95％。2的水解可定量提供KDR激酶抑制剂1。描述了还原环化反应的检查和条件的优化。
• Synthesis of 5-Substituted-1<i>H</i>-indol-2-yl-1<i>H</i>-quinolin-2-ones:  A Novel Class of KDR Kinase Inhibitors
  作者：Jeffrey T. Kuethe、Audrey Wong、Chuanxing Qu、Jacqueline Smitrovich、Ian W. Davies、David L. Hughes

  DOI：10.1021/jo0480545

  日期：2005.4.1

  A number of approaches for the synthesis of the 1H-indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitor 1 are described. The preparation and reaction of trimethylsilylnitrobenzene 26 with 2-methoxy-3-quinolinecarboxaldehyde 28 afforded alcohol 30, which was the key intermediate for the preparation of the target compounds. Conversion of alcohol 30 to either nitroketone 36 or nitrostyrene 45 set the stage for reductive cyclization and the formation of indole 25. The quinolin-2-one functionality was unmasked in the last step to provide compound 1 in 56-60% overall yield from readily available starting materials.
• EP1610614A2
  申请人：——

  公开号：EP1610614A2

  公开（公告）日：2006-01-04
• Formulations for tyrosine kinase inhibitors
  申请人：Karki B. Shyam

  公开号：US20060093666A1

  公开（公告）日：2006-05-04

  The present invention is related to a powder, powder blend or granulation formulation of 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one, a tyrosine kinase inhibitor, which is adapted for reconstitution with a diluent. This invention is also related to a prepared aqueous suspension, or dispersion, formulation, particularly to a stable oral pharmaceutical formulation, comprising granules of 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one mixed with a diluent. Additionally, the present invention is related to the method of preparing these formulations.
• [EN] FORMULATIONS FOR TYROSINE KINASE INHIBITORS<br/>[FR] FORMULATIONS POUR INHIBITEURS DE LA TYROSINE KINASE
  申请人：MERCK & CO INC

  公开号：WO2004087651A2

  公开（公告）日：2004-10-14

  The present invention is related to a powder, powder blend or granulation formulation of 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one, a tyrosine kinase inhibitor, which is adapted for reconstitution with a diluent. This invention is also related to a prepared aqueous suspension, or dispersion, formulation, particularly to a stable oral pharmaceutical formulation, comprising granules of 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one mixed with a diluent. Additionally, the present invention is related to the method of preparing these formulations.