Methyl 4-(8-tert-butyl-3-ethoxycarbonyl-2-oxochromen-6-yl)-2,7,7-trimethyl-5-oxo-1,4,6,8-tetrahydroquinoline-3-carboxylate | 1416403-26-3

• 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 4-(8-tert-butyl-3-ethoxycarbonyl-2-oxochromen-6-yl)-2,7,7-trimethyl-5-oxo-1,4,6,8-tetrahydroquinoline-3-carboxylate
• 英文别名: methyl 4-(8-tert-butyl-3-ethoxycarbonyl-2-oxochromen-6-yl)-2,7,7-trimethyl-5-oxo-1,4,6,8-tetrahydroquinoline-3-carboxylate
• CAS: 1416403-26-3
• 化学式: C₃₀H₃₅NO₇
• 分子量: 521.61
• InChiKey: QNPVRNGVCVENGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-叔丁基苯酚 在 哌啶 、 ammonium acetate 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 6.5h， 生成 Methyl 4-(8-tert-butyl-3-ethoxycarbonyl-2-oxochromen-6-yl)-2,7,7-trimethyl-5-oxo-1,4,6,8-tetrahydroquinoline-3-carboxylate
  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

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.