dimethyl-2,2 carbethoxy-6 furo<2,3-f>-2H-chromene | 76258-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: dimethyl-2,2 carbethoxy-6 furo<2,3-f>-2H-chromene
• 英文别名: ethyl 7,7-dimethyl-7H-furo[2,3-f]chromene-2-carboxylate；Ethyl 7,7-dimethylfuro[2,3-f]chromene-2-carboxylate
• CAS: 76258-64-5
• 化学式: C₁₆H₁₆O₄
• 分子量: 272.301
• InChiKey: GCWBFLXVZPXHJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  48.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dimethyl-2,2 carbethoxy-6 furo<2,3-f>-2H-chromene 在 sodium hydroxide 作用下， 以90%的产率得到7,7-Dimethylfuro[2,3-f]chromene-2-carboxylic acid
  参考文献：
  名称：

  Rene, Loic; Faulques, Michelle; Royer, Rene, Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1149 - 1150

  摘要：

  DOI：
• 作为产物：
  描述：

  5-羟基-2,2-二甲基-2H-色烯-6-甲醛 、 溴乙酸乙酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以72%的产率得到dimethyl-2,2 carbethoxy-6 furo<2,3-f>-2H-chromene
  参考文献：
  名称：

  Diversity-oriented generation and biological evaluation of new chemical scaffolds bearing a 2,2-dimethyl-2H-chromene unit: Discovery of novel potent ANO1 inhibitors

  摘要：

  Chemical territory bearing a 2,2-dimethyl-2H-chromene motif was expanded by utilizing an o-hydroxy aldehyde group of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde as a synthetic handle to install distinctive morphology and functionality of each scaffold. Cell based assays and in silico docking analysis led us to discover that these new compounds exhibit inhibitory effect on anoctamin1 (ANO1). ANO1 is amplified and highly ex-pressed in various carcinomas including prostate cancer, esophageal cancer, breast cancer, and pancreatic cancer. Biological assays revealed that (E)-1-(7,7-dimethyl-7H-furo[2,3-f]chromen-2-yl)-3-(1H-pyrrol-2-yl)prop-2-en-1-one (3n, Ani-FCC) is a novel, potent and selective ANO1 inhibitor with an IC50 value of 1.23 mu M. 3n showed 144 times stronger activity on ANO1 inhibition than ANO2 inhibition and did not alter the chloride channel activity of CFTR and the intracellular calcium signaling. Notably, 3n strongly decreased cell viability of PC-3 and FaDu cells expressing high levels of ANO1 with a decrease in ANO1 protein levels. In addition, 3n significantly enhanced apoptosis via activation of caspase 3 and cleavage of PARP in PC-3 and FaDu cells. This study shows that a novel ANO1 inhibitor, 3n, can be a potential candidate for the treatment of cancers over -expressing ANO1, such as prostate cancer and esophageal cancer.

  DOI：

  10.1016/j.bioorg.2020.104000

文献信息

• Averbeck; Moradi; Faulques, European Journal of Medicinal Chemistry, 1983, vol. 18, # 1, p. 15 - 21
  作者：Averbeck、Moradi、Faulques、et al.

  DOI：——

  日期：——
• Rene, Loic; Faulques, Michelle; Royer, Rene, Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1149 - 1150
  作者：Rene, Loic、Faulques, Michelle、Royer, Rene

  DOI：——

  日期：——
• Diversity-oriented generation and biological evaluation of new chemical scaffolds bearing a 2,2-dimethyl-2H-chromene unit: Discovery of novel potent ANO1 inhibitors
  作者：Yohan Seo、Jiwon Choi、Jeong Hwa Lee、Tae Gun Kim、So-hyeon Park、Gyoonhee Han、Wan Namkung、Ikyon Kim

  DOI：10.1016/j.bioorg.2020.104000

  日期：2020.8

  Chemical territory bearing a 2,2-dimethyl-2H-chromene motif was expanded by utilizing an o-hydroxy aldehyde group of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde as a synthetic handle to install distinctive morphology and functionality of each scaffold. Cell based assays and in silico docking analysis led us to discover that these new compounds exhibit inhibitory effect on anoctamin1 (ANO1). ANO1 is amplified and highly ex-pressed in various carcinomas including prostate cancer, esophageal cancer, breast cancer, and pancreatic cancer. Biological assays revealed that (E)-1-(7,7-dimethyl-7H-furo[2,3-f]chromen-2-yl)-3-(1H-pyrrol-2-yl)prop-2-en-1-one (3n, Ani-FCC) is a novel, potent and selective ANO1 inhibitor with an IC50 value of 1.23 mu M. 3n showed 144 times stronger activity on ANO1 inhibition than ANO2 inhibition and did not alter the chloride channel activity of CFTR and the intracellular calcium signaling. Notably, 3n strongly decreased cell viability of PC-3 and FaDu cells expressing high levels of ANO1 with a decrease in ANO1 protein levels. In addition, 3n significantly enhanced apoptosis via activation of caspase 3 and cleavage of PARP in PC-3 and FaDu cells. This study shows that a novel ANO1 inhibitor, 3n, can be a potential candidate for the treatment of cancers over -expressing ANO1, such as prostate cancer and esophageal cancer.