3-hydroxy-7-(3-methoxy-phenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-hydroxy-7-(3-methoxy-phenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione
• 英文别名: 3-hydroxy-7-(3-methoxyphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione
• 化学式: C₁₃H₁₀N₂O₅
• 分子量: 274.233
• InChiKey: AXJFPTUZOOOBQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  92
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲氧基苯乙腈 在 palladium diacetate 、 sodium hydroxide 、 敌草腈 、 sodium methylate 、 三苯基膦 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.0h， 生成 3-hydroxy-7-(3-methoxy-phenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione
  参考文献：
  名称：

  The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors

  摘要：

  Flap endonuclease-1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. Sensitization to DNA damaging agents is a potential method for the improvement of the therapeutic window of traditional chemotherapeutics. In this paper, we describe the identification and SAR of a series of low nanomolar FEN1 inhibitors. Over 1000-fold specificity was achieved against a related endonuclease, xeroderma pigmentosum G (XPG). Two compounds from this series significantly potentiate the action of methyl methanesulfonate (MMS) and temozolamide in a bladder cancer cell line (T24). To our knowledge, these are the most potent endonuclease inhibitors reported to date. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.086

文献信息

• Cyclic N-Hydroxy Imides as Inhibitors of Flap Endonuclease and Uses Thereof
  申请人：Tumey Lawrence N.

  公开号：US20080287465A1

  公开（公告）日：2008-11-20

  Acrylic n-hydroxy imides and their use in pharmaceutical compositions and in the inhibition of flap endonuclease are disclosed.

  本发明揭示了丙烯酸n-羟基亚酰亚胺及其在制药组合物和抑制皱褶内切酶方面的应用。
• US7947691B2
  申请人：——

  公开号：US7947691B2

  公开（公告）日：2011-05-24
• [EN] CYCLIC N-HYDROXY IMIDES AS INHIBITORS OF FLAP ENDONUCLEASE AND USES THEREOF<br/>[FR] N-HYDROXY-IMIDES SERVANT D'INHIBITEURS DE LA FLAP-ENDONUCLEASE ET LEURS UTILISATIONS
  申请人：ATHERSYS INC

  公开号：WO2006014647A2

  公开（公告）日：2006-02-09

  Acylic n-hydroxy imides and their use in pharmaceutical compositions and in the inhibition of flap endonuclease are disclosed.
• The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors
  作者：L. Nathan Tumey、David Bom、Bayard Huck、Elizabeth Gleason、Jianmin Wang、Daniel Silver、Kurt Brunden、Sherry Boozer、Stephen Rundlett、Bruce Sherf、Steven Murphy、Tom Dent、Christina Leventhal、Andrew Bailey、John Harrington、Youssef L. Bennani

  DOI：10.1016/j.bmcl.2004.10.086

  日期：2005.1

  Flap endonuclease-1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. Sensitization to DNA damaging agents is a potential method for the improvement of the therapeutic window of traditional chemotherapeutics. In this paper, we describe the identification and SAR of a series of low nanomolar FEN1 inhibitors. Over 1000-fold specificity was achieved against a related endonuclease, xeroderma pigmentosum G (XPG). Two compounds from this series significantly potentiate the action of methyl methanesulfonate (MMS) and temozolamide in a bladder cancer cell line (T24). To our knowledge, these are the most potent endonuclease inhibitors reported to date. (C) 2004 Elsevier Ltd. All rights reserved.