9-tert-butyl-2-[(E)-3-oxo-3-thiophen-2-ylprop-1-enyl]-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one | 1003869-34-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 9-tert-butyl-2-[(E)-3-oxo-3-thiophen-2-ylprop-1-enyl]-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one
• CAS: 1003869-34-8
• 化学式: C₂₇H₂₄N₂O₂S
• 分子量: 440.566
• InChiKey: XKBGVELRROOPMH-YRNVUSSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9-tert-butyl-2-iodo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 、 3-二甲基氨基-1-(噻吩基)-1-丙酮盐酸盐 在 palladium diacetate 三乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以34%的产率得到9-tert-butyl-2-[(E)-3-oxo-3-thiophen-2-ylprop-1-enyl]-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one
  参考文献：
  名称：

  2-(3-Aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: A New Antileishmanial Chemotype

  摘要：

  A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI(50) < 1 mu M) as well as on parasites in infected macrophages.

  DOI：

  10.1021/jm7012166

文献信息

• 2-(3-Aryl-3-oxopropen-1-yl)-9-<i>tert</i>-butyl-paullones: A New Antileishmanial Chemotype
  作者：Christina Reichwald、Orly Shimony、Ute Dunkel、Nina Sacerdoti-Sierra、Charles L. Jaffe、Conrad Kunick

  DOI：10.1021/jm7012166

  日期：2008.2.1

  A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI(50) < 1 mu M) as well as on parasites in infected macrophages.