ethyl 2-((furan-2-ylmethyl)amino)cyclooct-1-ene-1-carboxylate | 1061736-16-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: ethyl 2-((furan-2-ylmethyl)amino)cyclooct-1-ene-1-carboxylate
• CAS: 1061736-16-0
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: VVOJQPUBIBCBKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  51.47
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  2-呋喃甲胺 、 2-氧-1-环辛烷羧酸 以 氯仿 为溶剂， 生成 ethyl 2-((furan-2-ylmethyl)amino)cyclooct-1-ene-1-carboxylate
  参考文献：
  名称：

  A Pairwise Chemical Genetic Screen Identifies New Inhibitors of Glucose Transport

  摘要：

  Oxidative phosphorylation (OXPHOS) and glycolysis are the two main pathways that control energy metabolism of a cell. The Warburg effect, in which glycolysis remains active even under aerobic conditions, is considered a key driver for cancer cell proliferation, malignancy, metastasis, and therapeutic resistance. To target aerobic glycolysis, we exploited the complementary roles of OXPHOS and glycolysis in ATP synthesis as the basis for a chemical genetic screen, enabling rapid identification of novel small-molecule inhibitors of facilitative glucose transport. Blocking mitochondrial electron transport with antimycin A or leucascandrolide A had little effect on highly glycolytic A549 lung carcinoma cells, but adding known glycolytic inhibitors 2-deoxy-D-glucose, iodoacetate or cytochalasin B, rapidly depleted intracellular ATP, displaying chemical synthetic lethality. Based on this principle, we exposed antimycin A-treated A549 cells to a newly synthesized 955 member diverse scaffold small-molecule library, screening for compounds that rapidly depleted ATP levels. Two compounds potently suppressed ATP synthesis, induced G1 cell-cycle arrest and inhibited lactate production. Pathway analysis revealed that these novel probes inhibited GLUT family of facilitative transmembrane transporters but, unlike cytochalasin B, had no effect on the actin cytoskeleton. Our work illustrated the utility of a pairwise chemical genetic screen for discovery of novel chemical probes, which would be useful not only to study the system-level organization of energy metabolism but could also facilitate development of drugs targeting upregulation of aerobic glycolysis in cancer.

  DOI：

  10.1016/j.chembiol.2010.12.015