4-(4-{N-[(2-amino-4-hydroxy-6-quinazolinyl)methyl]prop-2-ynylamino}phenyl)butyric acid | 101248-33-3

• 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: 4-(4-{N-[(2-amino-4-hydroxy-6-quinazolinyl)methyl]prop-2-ynylamino}phenyl)butyric acid
• 英文别名: 4-[4-[(2-amino-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]phenyl]butanoic acid
• CAS: 101248-33-3
• 化学式: C₂₂H₂₂N₄O₃
• 分子量: 390.442
• InChiKey: JVLZOKNUMMJDQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(4-氨基苯)丁酸甲酯 在 sodium hydroxide 、 potassium carbonate 、 calcium carbonate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 46.5h， 生成 4-(4-{N-[(2-amino-4-hydroxy-6-quinazolinyl)methyl]prop-2-ynylamino}phenyl)butyric acid
  参考文献：
  名称：

  Quinazoline antifolates inhibiting thymidylate synthase. Variation of the amino acid

  摘要：

  Five new analogues (1c-g) of the antifolate N10-propargyl-5,8-dideazafolic acid (1a) are described in which the benzoyl-L-glutamate moiety was replaced by benzoic acid (desglutamyl-N10-propargyl-5,8-dideazafolic acid), benzoyl-L-aspartate, 4-phenylbutyrate, benzoylglycine, and benzoyl-L-alanine. The esters of the appropriate 4-aminophenyl (benzoyl) starting materials were sequentially alkylated upon nitrogen, first with a propargyl halide and then with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide. Saponification of the antifolate esters so produced gave the desired analogues. The new derivatives (1c-g) and also the known diethyl ester of 1a (1b) were tested for their inhibition of purified L1210 thymidylate synthase (TS) and for their inhibition of the growth of L1210 cells in culture. The TS inhibition of the analogues 1b-g was estimated by calculating the inverse relative potency, defined as the ratio IC50(compound)/IC50(1a). The results obtained were as follows: greater than 62, 84, 9, 333, 21, and 5, respectively. All were thus less inhibitory than 1a. None of the compounds improved upon 1a in inhibiting the growth of L1210 cells in culture.

  DOI：

  10.1021/jm00156a033

文献信息

• Quinazoline antifolates inhibiting thymidylate synthase. Variation of the amino acid
  作者：Terence R. Jones、Michael J. Smithers、Richard F. Betteridge、Michael A. Taylor、Ann L. Jackman、A. Hilary Calvert、Lawrence C. Davies、Kenneth R. Harrap

  DOI：10.1021/jm00156a033

  日期：1986.6

  Five new analogues (1c-g) of the antifolate N10-propargyl-5,8-dideazafolic acid (1a) are described in which the benzoyl-L-glutamate moiety was replaced by benzoic acid (desglutamyl-N10-propargyl-5,8-dideazafolic acid), benzoyl-L-aspartate, 4-phenylbutyrate, benzoylglycine, and benzoyl-L-alanine. The esters of the appropriate 4-aminophenyl (benzoyl) starting materials were sequentially alkylated upon nitrogen, first with a propargyl halide and then with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide. Saponification of the antifolate esters so produced gave the desired analogues. The new derivatives (1c-g) and also the known diethyl ester of 1a (1b) were tested for their inhibition of purified L1210 thymidylate synthase (TS) and for their inhibition of the growth of L1210 cells in culture. The TS inhibition of the analogues 1b-g was estimated by calculating the inverse relative potency, defined as the ratio IC50(compound)/IC50(1a). The results obtained were as follows: greater than 62, 84, 9, 333, 21, and 5, respectively. All were thus less inhibitory than 1a. None of the compounds improved upon 1a in inhibiting the growth of L1210 cells in culture.