N-<1,2-dihydro-1-oxo-9-<2-(trimethylsilyl)ethynyl>benzoquinazolin-3-yl>pivalamide | 139988-20-8

• 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: N-<1,2-dihydro-1-oxo-9-<2-(trimethylsilyl)ethynyl>benzoquinazolin-3-yl>pivalamide
• 英文别名: N-(1,2-dihydro-1-oxo-9-(2-(trimethylsilyl)ethynyl)benzo[f]quinazolin-3-yl)pivalamide；N-(1,2-dihydro-1-oxo-9-(trimethylsilylethynyl)benzo[f]quinazolin-3-yl)pivalamide；2,2-dimethyl-N-[1-oxo-9-(2-trimethylsilylethynyl)-2H-benzo[f]quinazolin-3-yl]propanamide
• CAS: 139988-20-8
• 化学式: C₂₂H₂₅N₃O₂Si
• 分子量: 391.545
• InChiKey: AVBFLDWZBMRUGQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  70.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-<1,2-dihydro-1-oxo-9-<2-(trimethylsilyl)ethynyl>benzoquinazolin-3-yl>pivalamide 在 palladium on activated charcoal 甲醇 、 sodium hydroxide 、 Lindlar's catalyst 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 5.67h， 生成 3-amino-9-ethylbenzo[f]quinazolin-1(2H)-one
  参考文献：
  名称：

  Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones

  摘要：

  The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo-[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 muM.

  DOI：

  10.1021/jm00068a004
• 作为产物：
  描述：

  7-溴-3,4-二氢-1H-2-萘酮 在 吡啶 、 palladium diacetate 、 N-溴代丁二酰亚胺(NBS) 、 sodium ethanolate 、 sodium hydride 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 乙腈 、 苯 为溶剂， 反应 49.75h， 生成 N-<1,2-dihydro-1-oxo-9-<2-(trimethylsilyl)ethynyl>benzoquinazolin-3-yl>pivalamide
  参考文献：
  名称：

  Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones

  摘要：

  The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo-[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 muM.

  DOI：

  10.1021/jm00068a004

文献信息

• Pharmaceutical compounds
  申请人：Burroughs Wellcome Co.

  公开号：US05405851A1

  公开（公告）日：1995-04-11

  The present invention relates to novel benzoquinazoline thymidylate synthase inhibitors, to pharmaceutical formulations containing them and to their use in medicine.

  本发明涉及新型苯并喹啉嘧啶酸合酶抑制剂、包含它们的制药配方以及它们在医学上的使用。
• Treatment of cancer with pharmaceutically active benzoquinazoline
  申请人：Glaxo Wellcome Inc.

  公开号：US05661155A1

  公开（公告）日：1997-08-26

  The present invention relates to bezoquinazoline thymidylate synthase inhibitors, to pharmaceutical formulations containing them and to their use in medicine.

  本发明涉及苯二氮杂喹嗪嘧啶酸合成酶抑制剂，含有它们的制药配方以及它们在医学上的使用。
• Pharmaceutically active benzoquinazoline compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP1199307B1

  公开（公告）日：2004-02-25
• Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones
  作者：William Pendergast、Jay V. Johnson、Scott H. Dickerson、Inderjit K. Dev、David S. Duch、Robert Ferone、William R. Hall、Joan Humphreys、Joseph M. Kelly、David C. Wilson

  DOI：10.1021/jm00068a004

  日期：1993.8

  The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo-[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 muM.