1-Methyl-3-phenoxymethyl-1H-quinoxalin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-Methyl-3-phenoxymethyl-1H-quinoxalin-2-one
• 英文别名: 1-Methyl-3-(phenoxymethyl)quinoxalin-2-one
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: GWPAOMLBXVILLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,3-二甲基-2-喹噁啉酮 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 苄基三乙基氯化铵 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 氯仿 为溶剂， 反应 10.5h， 生成 1-Methyl-3-phenoxymethyl-1H-quinoxalin-2-one
  参考文献：
  名称：

  Structure−Activity Studies of Substituted Quinoxalinones as Multiple-Drug-Resistance Antagonists

  摘要：

  A significant problem in the clinical treatment of cancer relates to the development of tumor resistance to many chemotherapeutic agents. Acquired drug resistance is often mediated through overexpression of membrane transport proteins that effectively efflux anticancer agents. Two of the best-studied transporters, P-glycoprotein (Pgp) and MRP1, have pharmacological properties that only partially overlap. In our search for improved drug-resistance antagonists, we have identified a family of substituted quinoxalines that selectively antagonizes Pgp over MRP1. Consequently, a focused library of congeners was designed and synthesized starting with a parent bromomethylquinoxalinone. This parent quinoxalinone was then condensed with a series of phenols to yield a family of substituted phenoxymethylquinoxalinones. These compounds were evaluated for their toxicity toward drug-sensitive MCF-7 breast carcinoma cells and for their abilities to antagonize Pgp and MRP1 in drug-resistant cell lines (NCI/ADR and MCF-7/VP, respectively). The results of this structure-activity study indicate that compounds with carbonyl substitutions of the phenoxy group tester, amide, or ketone moieties) demonstrate excellent antagonism of Pgp while having relatively low toxicity toward drug-sensitive cells. Importantly, none of these compounds antagonized MRP1. Because of their transporter selectivity, we predict that substituted quinoxalinones may be more effective MDR modulators in vivo than are nonselective transporter antagonists.

  DOI：

  10.1021/jm000282d

文献信息

• Novel compounds for enhancing chemotherapy
  申请人：——

  公开号：US20020013322A1

  公开（公告）日：2002-01-31

  The present invention provides chemical compounds, pharmaceutical compositions, and methods for increasing the therapeutic efficacy of drugs. Specifically, the invention provides compounds and compositions for inhibiting drug transport proteins that efflux therapeutic agents from cells, and to methods for using these compounds and pharmaceutical compositions to increase the efficacy of the therapeutic agents that are effluxed by these drug transport proteins.

  本发明提供了化学化合物、药物组合物和方法，用于增强药物的治疗效果。具体地，本发明提供了抑制药物转运蛋白的化合物和组合物，这些蛋白从细胞中排出治疗剂量的药物，并提供使用这些化合物和药物组合物的方法，以增加被这些药物转运蛋白排出的治疗剂量的药物的疗效。
• Compounds for enhancing chemotherapy
  申请人：The Penn State Research Foundation.

  公开号：US20030105122A1

  公开（公告）日：2003-06-05

  The present invention provides 2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-ylamines, of the formula: 1 or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , and R 7 are as defined herein. Also disclosed are pharmaceutical compositions comprising such compounds, and methods for using the compounds to increase the therapeutic efficacy of drugs.

  本发明提供了2,3-二氢-1H-吡咯并[2,3-b]喹啉-4-胺，化学式为：1或其药学上可接受的盐，其中R1、R2、R3和R7如本文所定义。还披露了包含这些化合物的药物组合物，以及使用这些化合物来增强药物的治疗效果的方法。
• NOVEL COMPOUNDS FOR ENHANCING CHEMOTHERAPY
  申请人：THE PENN STATE RESEARCH FOUNDATION

  公开号：EP1272479A2

  公开（公告）日：2003-01-08
• US6537993B2
  申请人：——

  公开号：US6537993B2

  公开（公告）日：2003-03-25
• US6693112B2
  申请人：——

  公开号：US6693112B2

  公开（公告）日：2004-02-17