diethyl N-<4-prop-2-ynylamino>benzoyl>-L-aspartate | 80014-78-4

• 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 N-<4-prop-2-ynylamino>benzoyl>-L-aspartate
• 英文别名: diethyl N-(4-{N-[(2-amino-4-hydroxy-6-quinazolinyl)methyl]prop-2-ynylamino}benzoyl)-L-aspartate；diethyl (2S)-2-[[4-[(2-amino-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]benzoyl]amino]butanedioate
• CAS: 80014-78-4
• 化学式: C₂₇H₂₉N₅O₆
• 分子量: 519.557
• InChiKey: HFXQUEFDEMRGDO-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diethyl N-<4-prop-2-ynylamino>benzoyl>-L-aspartate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以72%的产率得到N-<4-prop-2-ynylamino>benzoyl>-L-aspartic 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
• 作为产物：
  描述：

  diethyl L-aspartate hydrochloride 在 palladium on activated charcoal 吡啶 、 2,6-二甲基吡啶 、 氢气 、 calcium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 145.5h， 生成 diethyl N-<4-prop-2-ynylamino>benzoyl>-L-aspartate
  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 derivatives, processes for their preparation, compositions containing them and their use as anti-cancer agents
  申请人：NATIONAL RESEARCH DEVELOPMENT CORPORATION

  公开号：EP0031237B1

  公开（公告）日：1984-10-17