diethyl (S)-2-(2,3-Dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)-glutarate | 139988-50-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl (S)-2-(2,3-Dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)-glutarate
• 英文别名: diethyl (S)-2-(2,3-dihydro-6-(((1,2-dihydro-3-methyl-1-oxobenzoquinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)glutarate；Diethyl (S)-2-(2,3-Dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl) glutarate；diethyl (S)-2-(2,3-dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)glutarate；diethyl (S)-2-(2,3-dihydro-6-{[(1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino}-3-oxo-1,2-benzisothiazol-2-yl)glutarate；diethyl (2S)-2-[6-[(3-methyl-1-oxo-2H-benzo[f]quinazolin-9-yl)methylamino]-3-oxo-1,2-benzothiazol-2-yl]pentanedioate
• CAS: 139988-50-4
• 化学式: C₃₀H₃₀N₄O₆S
• 分子量: 574.657
• InChiKey: CGHHTYSVAWNNNT-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  diethyl (S)-2-(2,3-Dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)-glutarate 生成 (S)-2-(2,3-dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)glutaric acid
  参考文献：
  名称：

  Pharmaceutically active benzoquinazoline compounds

  摘要：

  公开号：

  EP1199307B1
• 作为产物：
  描述：

  4,4'-dinitro-2,2'-disulfanediyl-bis-benzoyl chloride 在 氯 、 铁粉 、 碳酸氢钠 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 生成 diethyl (S)-2-(2,3-Dihydro-6-(((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methyl)amino)-3-oxo-1,2-benzisothiazol-2-yl)-glutarate
  参考文献：
  名称：

  Benzo[f]quinazoline Inhibitors of Thymidylate Synthase: Methyleneamino-Linked Aroylglutamate Derivatives

  摘要：

  Syntheses of several new inhibitors of thymidylate synthase (TS) structurally related to folic acid are described in which the pterin portion of the folate molecule is replaced by a benzo[f]quinazoline moiety, but which retain the natural methyleneamino link to the benzoylglutamate side chain. The effect on enzyme activity and cytotoxicity of various changes in the structure of the (p-aminobenzoyl)glutamate side chain are reported. Replacement of the benzamide portion of the (p-aminobenzoyl)glutamate moiety with 2-fluorobenzamido, 2-isoindolinyl, 1,2-benzisothiazol-2-yl, and 2-thenamido moieties varied in effect from a 9-fold diminution of TS activity to a 5-fold enhancement, while cytotoxic potency on SW-480 and MCF-7 tumor lines showed increases ranging from 3.6-to 450-fold. The detrimental effect on enzyme activity and cytotoxicity of alkyl substitution on the PABA nitrogen is confirmed for these compounds, in contrast with several series of previously reported quinazoline antifolates (2). Substitution of a C3-methyl substituent for 3-amino had little effect on TS activity but was beneficial in terms of solubility and cytotoxicity. The excellent combination of TS inhibitory activity, FPGS substrate activity, and affinity for the reduced folate transport system in the most potent of these derivatives, 3e, resulted in IC50 values of 0.2-0.8 nM against these tumor lines.

  DOI：

  10.1021/jm00032a019

文献信息

• US6306865B1
  申请人：——

  公开号：US6306865B1

  公开（公告）日：2001-10-23