1-(2-(4-fluorophenoxy)acetyl)-N-methylindoline-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(2-(4-fluorophenoxy)acetyl)-N-methylindoline-2-carboxamide
• 英文别名: 1-[2-(4-fluorophenoxy)acetyl]-N-methyl-2,3-dihydroindole-2-carboxamide
• 化学式: C₁₈H₁₇FN₂O₃
• 分子量: 328.343
• InChiKey: BHRBERXUBCBIRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氟苯氧乙酸 、 吲哚啉-2-羧酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(2-(4-fluorophenoxy)acetyl)-N-methylindoline-2-carboxamide
  参考文献：
  名称：

  Discovery of Indoline-2-carboxamide Derivatives as a New Class of Brain-Penetrant Inhibitors of Trypanosoma brucei

  摘要：

  There is an urgent need for new, brain penetrant small molecules that target the central nervous system second stage of human African trypanosomiasis (HAT). We report that a series of novel indoline-2carboxamides have been identified as inhibitors of Trypanosoma brucei from screening of a focused protease library against Trypanosoma brucei brucei in culture. We describe the optimization and characterization of this series. Potent antiproliferative activity was observed. The series demonstrated excellent pharmacokinetic properties, full cures in a stage 1 mouse model of HAT, and a partial cure in a stage 2 mouse model of HAT. Lack of tolerability prevented delivery of a fully curative regimen in the stage 2 mouse model and thus further progress of this series.

  DOI：

  10.1021/acs.jmedchem.5b00596

文献信息

• Discovery of Indoline-2-carboxamide Derivatives as a New Class of Brain-Penetrant Inhibitors of <i>Trypanosoma brucei</i>
  作者：Laura A. T. Cleghorn、Sébastien Albrecht、Laste Stojanovski、Frederick R. J. Simeons、Suzanne Norval、Robert Kime、Iain T. Collie、Manu De Rycker、Lorna Campbell、Irene Hallyburton、Julie A. Frearson、Paul G. Wyatt、Kevin D. Read、Ian H. Gilbert

  DOI：10.1021/acs.jmedchem.5b00596

  日期：2015.10.8

  There is an urgent need for new, brain penetrant small molecules that target the central nervous system second stage of human African trypanosomiasis (HAT). We report that a series of novel indoline-2carboxamides have been identified as inhibitors of Trypanosoma brucei from screening of a focused protease library against Trypanosoma brucei brucei in culture. We describe the optimization and characterization of this series. Potent antiproliferative activity was observed. The series demonstrated excellent pharmacokinetic properties, full cures in a stage 1 mouse model of HAT, and a partial cure in a stage 2 mouse model of HAT. Lack of tolerability prevented delivery of a fully curative regimen in the stage 2 mouse model and thus further progress of this series.