2-Cyclopropyl-5-methylfuran-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: 2-Cyclopropyl-5-methylfuran-3-carboxylic acid
• 化学式: C₉H₁₀O₃
• 分子量: 166.177
• InChiKey: JCAOXOSJMZMNRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Cyclopropyl-5-methylfuran-3-carboxylic acid 、 2-amino-N-(2-(dimethylamino)ethyl)-3-(3′-(trifluoromethyl)biphenyl-4-yl)propanamide hydrochloride 、 三氟乙酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 、 水 、 乙腈 为溶剂， 反应 2.0h， 生成 2-cyclopropyl-N-(1-(2-(dimethylamino)ethylamino)-1-oxo-3-(3'-(trifluoromethyl)biphenyl-4-yl)propan-2-yl)-5-methylfuran-3-carboxamide trifluoroacetic acid
  参考文献：
  名称：

  Discovery of Potent KIFC1 Inhibitors Using a Method of Integrated High-Throughput Synthesis and Screening

  摘要：

  KIFC1 (HSET), a member of the kinesin-14 family of motor proteins, plays an essential role in centrosomal bundling in cancer cells, but its function is not required for normal diploid cell division. To explore the potential of KIFC1 as a therapeutic target for human cancers, a series of potent KIFC1 inhibitors featuring a phenylalanine scaffold was developed from hits identified through high-throughput screening (HTS). Optimization of the initial hits combined both design-synthesis-test cycles and an integrated high-throughput synthesis and biochemical screening method. An important aspect of this integrated method was the utilization of DMSO stock solutions of compounds registered in the corporate compound collection as synthetic reactants. Using this method, over 1500 compounds selected for structural diversity were quickly assembled in assay-ready 384-well plates and were directly tested after the necessary dilutions. Our efforts led to the discovery of a potent KIFC1 inhibitor, AZ82, which demonstrated the desired centrosome declustering mode of action in cell studies.

  DOI：

  10.1021/jm501179r