3-Hydroxy-7-p-tolyl-1H-furo[3,2-d]pyrimidine-2,4-dione | 824983-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-Hydroxy-7-p-tolyl-1H-furo[3,2-d]pyrimidine-2,4-dione
• 英文别名: 3-Hydroxy-7-(4-methylphenyl)furo[3,2-d]pyrimidine-2,4(1H,3H)-dione；3-hydroxy-7-(4-methylphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione
• CAS: 824983-99-5
• 化学式: C₁₃H₁₀N₂O₄
• 分子量: 258.233
• InChiKey: FFGCIABZEPVWCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  82.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对甲基苯乙腈 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-p-tolyl-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

• 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.