methyl 6-formyl-8-isopropyl-2-oxo-2H-chromene-3-carboxylate | 1416403-06-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: methyl 6-formyl-8-isopropyl-2-oxo-2H-chromene-3-carboxylate
• 英文别名: Ethyl 8-tert-butyl-6-formyl-2-oxochromene-3-carboxylate；ethyl 8-tert-butyl-6-formyl-2-oxochromene-3-carboxylate
• CAS: 1416403-06-9
• 化学式: C₁₇H₁₈O₅
• 分子量: 302.327
• InChiKey: DGWDIFPKMGDGQL-UHFFFAOYSA-N

物化性质

• 沸点：
  467.6±45.0 °C(predicted)
• 密度：
  1.221±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 6-formyl-8-isopropyl-2-oxo-2H-chromene-3-carboxylate 、 乙酰乙酸甲酯 在 ammonium acetate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以82%的产率得到Dimethyl 4-(8-tert-butyl-3-ethoxycarbonyl-2-oxochromen-6-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Discovery of Coumarin–Dihydropyridine Hybrids as Bone Anabolic Agents

  摘要：

  The concept of molecular hybridization led us to discover a novel series of coumarin- dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds 10, 14, 18, and 22 showed significant activity at picomolar concentrations. A series of other in vitro data strongly suggested compound 18 as the most promising bone anabolic agent, which was further evaluated for in vivo studies. From these studies compound 18 proved to be useful, which at low oral dose of 1 (mg/kg)/day body weight increased bone mass density and volume, expression of osteogenic genes (RUNX2, BMP-2, and Coll), bone formation rate (BFR), and mineral apposition rate (MAR), improved the trabecular microarchitecture, and decreased bone turn over markers in an ovariectomized rodent model for postmenopausal osteoporosis.

  DOI：

  10.1021/jm301281e
• 作为产物：
  描述：

  2-叔丁基苯酚 在 哌啶 、 乌洛托品 作用下， 以 乙醇 为溶剂， 生成 methyl 6-formyl-8-isopropyl-2-oxo-2H-chromene-3-carboxylate
  参考文献：
  名称：

  香豆素-咪唑并[1,2- a ]吡啶衍生物的 设计，合成及体外评价抗癌性骨质疏松症†

  摘要：

  利用银（I）催化的Groebke-Blackburn-Bienayme多组分反应合成了一系列具有重要生物学意义的6-（咪唑并[1,2 - a ]吡啶-2-基）-2 H -chromen-2-one衍生物。通过碱性磷酸酶测定法和茜素红-S染色测定法在原发性颅盖骨成骨细胞中测试了合成的化合物的可能的骨保护特性。此外，通过qPCR测量活性化合物6h，6l和6o对成骨基因BMP2，RUNX2，COL1和OCN表达的影响。在三种有前途的化合物中，每升6升6a和6o通过线粒体去极化显着诱导了MDA-MB-231癌细胞的凋亡，而不影响正常细胞。在体外骨转移共培养模型中，我们研究了香豆素-咪唑并[1,2- a ]吡啶杂化物逆转MDA-MB-231癌细胞对成骨细胞分化的负面影响的能力。结果说明了设计的杂交体重建骨骼稳态的潜力。这些发现证明了新合成的杂种作为先导分子的重要性，既具有抗骨质疏松性又具有抗癌性，可

  DOI：

  10.1039/c6ra15674f

文献信息

• Discovery of Coumarin–Dihydropyridine Hybrids as Bone Anabolic Agents
  作者：Koneni V. Sashidhara、Manoj Kumar、Vikram Khedgikar、Priyanka Kushwaha、Ram K. Modukuri、Abdhesh Kumar、Jyoti Gautam、Divya Singh、Balasubramaniam Sridhar、Ritu Trivedi

  DOI：10.1021/jm301281e

  日期：2013.1.10

  The concept of molecular hybridization led us to discover a novel series of coumarin- dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds 10, 14, 18, and 22 showed significant activity at picomolar concentrations. A series of other in vitro data strongly suggested compound 18 as the most promising bone anabolic agent, which was further evaluated for in vivo studies. From these studies compound 18 proved to be useful, which at low oral dose of 1 (mg/kg)/day body weight increased bone mass density and volume, expression of osteogenic genes (RUNX2, BMP-2, and Coll), bone formation rate (BFR), and mineral apposition rate (MAR), improved the trabecular microarchitecture, and decreased bone turn over markers in an ovariectomized rodent model for postmenopausal osteoporosis.
• Design, synthesis and in vitro evaluation of coumarin–imidazo[1,2-a]pyridine derivatives against cancer induced osteoporosis
  作者：Koneni V. Sashidhara、L. Ravithej Singh、Dharmendra Choudhary、Ashutosh Arun、Sampa Gupta、Sulekha Adhikary、Gopala Reddy Palnati、Rituraj Konwar、Ritu Trivedi

  DOI：10.1039/c6ra15674f

  日期：——

  Out of three promising compounds, 6l and 6o significantly induced apoptosis in MDA-MB-231 cancer cells via mitochondrial depolarisation without affecting normal cells. In an in vitro co-culture model of bone metastasis, we investigated the ability of coumarin–imidazo[1,2-a]pyridine hybrids to reverse the negative impact of MDA-MB-231 cancer cells on osteoblast differentiation. The results illustrate

  利用银（I）催化的Groebke-Blackburn-Bienayme多组分反应合成了一系列具有重要生物学意义的6-（咪唑并[1,2 - a ]吡啶-2-基）-2 H -chromen-2-one衍生物。通过碱性磷酸酶测定法和茜素红-S染色测定法在原发性颅盖骨成骨细胞中测试了合成的化合物的可能的骨保护特性。此外，通过qPCR测量活性化合物6h，6l和6o对成骨基因BMP2，RUNX2，COL1和OCN表达的影响。在三种有前途的化合物中，每升6升6a和6o通过线粒体去极化显着诱导了MDA-MB-231癌细胞的凋亡，而不影响正常细胞。在体外骨转移共培养模型中，我们研究了香豆素-咪唑并[1,2- a ]吡啶杂化物逆转MDA-MB-231癌细胞对成骨细胞分化的负面影响的能力。结果说明了设计的杂交体重建骨骼稳态的潜力。这些发现证明了新合成的杂种作为先导分子的重要性，既具有抗骨质疏松性又具有抗癌性，可