5-methoxy-N-[3-pyrimidin-5-yl-5-(trifluoromethoxy)phenyl]-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide | 1359945-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-methoxy-N-[3-pyrimidin-5-yl-5-(trifluoromethoxy)phenyl]-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
• CAS: 1359945-83-7
• 化学式: C₂₂H₁₆F₆N₄O₃
• 分子量: 498.384
• InChiKey: XKJXIVGDDDNJDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  3-溴-5-(三氟甲氧基)苯胺 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 120.0 ℃ 、1.6 MPa 条件下， 反应 2.0h， 生成 5-methoxy-N-[3-pyrimidin-5-yl-5-(trifluoromethoxy)phenyl]-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
  参考文献：
  名称：

  A Divergent SAR Study Allows Optimization of a Potent 5-HT_2c Inhibitor to a Promising Antimalarial Scaffold

  摘要：

  From the 13 533 chemical structures published by GlaxoSmithKline in 2010, we identified 47 quality starting points for lead optimization. One of the most promising hits was the TCMDC-139046, a molecule presenting an indoline core, which is well-known for its anxiolytic properties by interacting with serotonin antagonist receptors 5-HT2. The inhibition of this target will complicate the clinical development of these compounds as antimalarials. Herein, we present the antimalarial profile of this series and our efforts to avoid interaction with this receptor, while maintaining a good antiparasitic potency. By using a double-divergent structure-activity relationship analysis, we have obtained a novel lead compound harboring an indoline core.

  DOI：

  10.1021/ml300008j

文献信息

• A Divergent SAR Study Allows Optimization of a Potent 5-HT_2c Inhibitor to a Promising Antimalarial Scaffold
  作者：Félix Calderón、Jaume Vidal-Mas、Jeremy Burrows、Juan Carlos de la Rosa、María Belén Jiménez-Díaz、Teresa Mulet、Sara Prats、Jorge Solana、Michael Witty、Francisco Javier Gamo、Esther Fernández

  DOI：10.1021/ml300008j

  日期：2012.5.10

  From the 13 533 chemical structures published by GlaxoSmithKline in 2010, we identified 47 quality starting points for lead optimization. One of the most promising hits was the TCMDC-139046, a molecule presenting an indoline core, which is well-known for its anxiolytic properties by interacting with serotonin antagonist receptors 5-HT2. The inhibition of this target will complicate the clinical development of these compounds as antimalarials. Herein, we present the antimalarial profile of this series and our efforts to avoid interaction with this receptor, while maintaining a good antiparasitic potency. By using a double-divergent structure-activity relationship analysis, we have obtained a novel lead compound harboring an indoline core.