6-(cyclopropylmethoxy)-3-oxobenzofuran | 1337856-52-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 6-(cyclopropylmethoxy)-3-oxobenzofuran
• 英文别名: 6-(Cyclopropylmethoxy)-1-benzofuran-3-one
• CAS: 1337856-52-6
• 化学式: C₁₂H₁₂O₃
• 分子量: 204.225
• InChiKey: SCVANVCBDCRVJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(cyclopropylmethoxy)-3-oxobenzofuran 在 potassium carbonate 、 potassium iodide 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.0h， 生成 (Z)-2-(4-((6-(cyclopropylmethoxy)-3-oxobenzofuran-2(3H)-ylidene)methyl)-2,6-dimethylphenoxy)acetic acid
  参考文献：
  名称：

  Discovery of the first-in-class dual PPARδ/γ partial agonist for the treatment of metabolic syndrome

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113807
• 作为产物：
  描述：

  6-羟基-2H-苯并呋喃-3-酮 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 6-(cyclopropylmethoxy)-3-oxobenzofuran
  参考文献：
  名称：

  Discovery of the first-in-class dual PPARδ/γ partial agonist for the treatment of metabolic syndrome

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113807

文献信息

• 一类PPARγ/δ双重激动剂、其制备方法及其作为药物的用途
  申请人：广东药科大学

  公开号：CN109369583A

  公开（公告）日：2019-02-22

  本发明涉及一类通式(I)所示的新型PPARγ/δ双重激动剂、其制备方法及含有该衍生物的药物组合物作为制备预防或/和治疗葡萄糖代谢异常或/和脂质代谢异常疾病的药物用途。所述的PPARγ/δ双重激动剂具有优异的体内降血糖活性及调节血脂作用，可应用于制备预防或/和治疗糖尿病、肥胖症、高血脂、动脉粥样硬化及脂肪肝等代谢综合症相关疾病的药物，具有广阔的应用前景。
• Design, synthesis, and biological evaluation studies of novel carboxylesterase 2 inhibitors for the treatment of irinotecan-induced delayed diarrhea
  作者：Zhongcheng Yang、Zhijun Cao、Wenxin Wang、Ya Chen、Wanqiu Huang、Shixuan Jiao、Siliang Chen、Lianru Chen、Yuxia Liu、Jianming Mao、Luyong Zhang、Zheng Li

  DOI：10.1016/j.bioorg.2023.106625

  日期：2023.9

  irinotecan. Nonetheless, there is a scarcity of selective and effective inhibitors that are suitable for irinotecan-induced delayed diarrhea. Following screening of the in-house library, the lead compound 01 was identified with potent inhibition on hCES2A, which was further optimized to obtain LK-44 with potent inhibitory activity (IC50 = 5.02 ± 0.67 μM) and high selectivity on hCES2A. Molecular docking

  人羧酸酯酶2（hCES2A）是分布在小肠和结肠中最重要的丝氨酸水解酶之一，在多种前药和酯的水解中起着至关重要的作用。越来越多的证据表明，抑制hCES2A可以有效减轻一些hCES2A底物药物引起的副作用，包括抗癌药物伊立替康引起的迟发性腹泻。尽管如此，仍然缺乏适用于伊立替康引起的迟发性腹泻的选择性且有效的抑制剂。经过内部文库筛选，确定先导化合物01对hCES2A具有强效抑制作用，进一步优化得到对hCES2A具有强效抑制活性（IC 50 = 5.02 ± 0.67 μM）和高选择性的LK-44 。分子对接和分子动力学模拟表明LK-44可以与hCES2A活性空腔周围的氨基酸形成稳定的氢键。抑制动力学研究结果表明， LK-44以混合抑制方式抑制hCES2A介导的FD水解， K i值为5.28 μM。值得注意的是，根据 MTT 测定， LK-44对 HepG2 细胞表现出低毒性。重要的是，体内研究表
• From a Natural Product Lead to the Identification of Potent and Selective Benzofuran-3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3β Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells
  作者：Irina N. Gaisina、Franck Gallier、Andrei V. Ougolkov、Ki H. Kim、Toru Kurome、Songpo Guo、Denise Holzle、Doris N. Luchini、Sylvie Y. Blond、Daniel D. Billadeau、Alan P. Kozikowski

  DOI：10.1021/jm801317h

  日期：2009.4.9

  Recent studies have demonstrated that glycogen synthase kinase 3 beta (GSK-3 beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3 beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3 beta and an enhanced selectivity against cycl in-dependent kinase 2 (CDK-2). Selected GSK-3 beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3 beta inhibitors 5 and 26 resulted in suppression of GSK-3 beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3 beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.
• Discovery of the first-in-class dual PPARδ/γ partial agonist for the treatment of metabolic syndrome
  作者：Zheng Li、Qiang Ren、Zongtao Zhou、Zongyu Cai、Bin Wang、Jing Han、Luyong Zhang

  DOI：10.1016/j.ejmech.2021.113807

  日期：2021.12