4-(benzyloxy)-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline | 1135035-16-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(benzyloxy)-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline
• 英文别名: 3-methyl-2-[[3-(oxan-4-ylmethoxy)phenoxy]methyl]-4-phenylmethoxyquinoline
• CAS: 1135035-16-3
• 化学式: C₃₀H₃₁NO₄
• 分子量: 469.58
• InChiKey: WDXXOAZKQDRPFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(benzyloxy)-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline 在 钯 氢气 、 silica gel 、 chloroform methanol 作用下， 以 Tetrahydrofuran ethanol 为溶剂， 反应 1.0h， 以to obtain 3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinolin-4(1H)-one (207 mg)的产率得到3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinolin-4(1H)-one
  参考文献：
  名称：

  QUINOLONE DERIVATIVE

  摘要：

  通过对NAD（P）H氧化酶抑制剂的广泛研究，本发明人发现，在2位具有被杂原子或类似物取代的烷基的喹诺酮衍生物具有优异的NAD（P）H氧化酶抑制活性，并完成了本发明。本发明的化合物具有基于NAD（P）H氧化酶抑制活性的反应性氧化物产生抑制活性，因此可用作预防和/或治疗糖尿病、糖耐量受损、高脂血症、脂肪肝、糖尿病并发症等代理。

  公开号：

  US20100256113A1
• 作为产物：
  描述：

  3-(tetrahydro-2H-pyran-4-ylmethoxy)phenol 、 4-(苄氧基)-2-(氯甲基)-3-甲基喹啉 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(benzyloxy)-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline
  参考文献：
  名称：

  Identification of 4-quinolone derivatives as inhibitors of reactive oxygen species production from human umbilical vein endothelial cells

  摘要：

  Oxidative stress is widely recognized as being associated with a number of disorders, including metabolic dysfunction and atherosclerosis. A series of substituted 4-quinolone derivatives were prepared and evaluated as inhibitors of reactive oxygen species (ROS) production from human umbilical vein endothelial cells (HUVECs). One compound in particular, 2-({[4-(3-hydroxy-3-methylbutoxy)pyridin-2-yl]oxy}-methyl)- 3-methylquinolin-4(1H)-one (25b), inhibited ROS production from HUVECs with an IC50 of 140 nM. This compound also exhibited low CYP2D6 inhibitory activity, high aqueous solubility, and good in vitro metabolic stability. An in vivo pharmacokinetic study of this compound in SD rats revealed high oral bioavailability and a long plasma half-life. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.015

文献信息

• QUINOLONE DERIVATIVE
  申请人：Onda Kenichi

  公开号：US20100256113A1

  公开（公告）日：2010-10-07

  As a result of extensive studies on NAD(P)H oxidase inhibitors, the present inventors found that a quinolone derivative having, at the 2-position, an alkyl group substituted with a heteroatom or the like has an excellent NAD(P)H oxidase inhibitory activity, and accomplished the present invention. The compound of the present invention has a reactive oxygen species production inhibitory activity based on the NAD(P)H oxidase inhibitory activity, and therefore can be used as an agent for preventing and/or treating diabetes, impaired glucose tolerance, hyperlipidemia, fatty liver, diabetic complications and the like.

  通过对NAD（P）H氧化酶抑制剂的广泛研究，本发明人发现，在2位具有被杂原子或类似物取代的烷基的喹诺酮衍生物具有优异的NAD（P）H氧化酶抑制活性，并完成了本发明。本发明的化合物具有基于NAD（P）H氧化酶抑制活性的反应性氧化物产生抑制活性，因此可用作预防和/或治疗糖尿病、糖耐量受损、高脂血症、脂肪肝、糖尿病并发症等代理。
• Quinolone derivative
  申请人：Onda Kenichi

  公开号：US08367702B2

  公开（公告）日：2013-02-05

  As a result of extensive studies on NAD(P)H oxidase inhibitors, the present inventors found that a quinolone derivative having, at the 2-position, an alkyl group substituted with a heteroatom or the like has an excellent NAD(P)H oxidase inhibitory activity, and accomplished the present invention. The compound of the present invention has a reactive oxygen species production inhibitory activity based on the NAD(P)H oxidase inhibitory activity, and therefore can be used as an agent for preventing and/or treating diabetes, impaired glucose tolerance, hyperlipidemia, fatty liver, diabetic complications and the like.

  由于对NAD（P）H氧化酶抑制剂的广泛研究，本发明人发现，在2位具有被杂原子或类似物取代的烷基基团的喹诺酮衍生物具有出色的NAD（P）H氧化酶抑制活性，并完成了本发明。本发明的化合物具有基于NAD（P）H氧化酶抑制活性的反应性氧化物产生抑制活性，因此可用作预防和/或治疗糖尿病、糖耐量受损、高脂血症、脂肪肝、糖尿病并发症等的药物。
• EP2194044
  申请人：——

  公开号：——

  公开（公告）日：——
• US8367702B2
  申请人：——

  公开号：US8367702B2

  公开（公告）日：2013-02-05
• Identification of 4-quinolone derivatives as inhibitors of reactive oxygen species production from human umbilical vein endothelial cells
  作者：Kenichi Onda、Fumie Narazaki、Naoki Ishibashi、Keita Nakanishi、Yuki Sawada、Ken-ichiro Imamura、Kazuhiro Momose、Shigetada Furukawa、Yoshiaki Shimada、Hiroyuki Moriguchi、Masamichi Yuda、Hiroshi Kayakiri、Mitsuaki Ohta

  DOI：10.1016/j.bmcl.2011.09.015

  日期：2011.11

  Oxidative stress is widely recognized as being associated with a number of disorders, including metabolic dysfunction and atherosclerosis. A series of substituted 4-quinolone derivatives were prepared and evaluated as inhibitors of reactive oxygen species (ROS) production from human umbilical vein endothelial cells (HUVECs). One compound in particular, 2-([4-(3-hydroxy-3-methylbutoxy)pyridin-2-yl]oxy}-methyl)- 3-methylquinolin-4(1H)-one (25b), inhibited ROS production from HUVECs with an IC50 of 140 nM. This compound also exhibited low CYP2D6 inhibitory activity, high aqueous solubility, and good in vitro metabolic stability. An in vivo pharmacokinetic study of this compound in SD rats revealed high oral bioavailability and a long plasma half-life. (C) 2011 Elsevier Ltd. All rights reserved.