{[5-cyano-2-(1-naphthyl)-6-phenyl-4-pyrimidinyl]-oxy}acetic acid | 119491-89-3

• 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: {[5-cyano-2-(1-naphthyl)-6-phenyl-4-pyrimidinyl]-oxy}acetic acid
• 英文别名: 2-(5-Cyano-2-naphthalen-1-yl-6-phenylpyrimidin-4-yl)oxyacetic acid
• CAS: 119491-89-3
• 化学式: C₂₃H₁₅N₃O₃
• 分子量: 381.39
• InChiKey: XOBBGSKTPLRHOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (5-Cyano-2-naphthalen-1-yl-6-phenyl-pyrimidin-4-yloxy)-acetic acid tert-butyl ester 在 三氟乙酸 作用下， 反应 16.0h， 生成 {[5-cyano-2-(1-naphthyl)-6-phenyl-4-pyrimidinyl]-oxy}acetic acid
  参考文献：
  名称：

  (Pyrimidinyloxy)acetic acids and pyrimidineacetic acids as a novel class of aldose reductase inhibitors

  摘要：

  Pyrimidineacetic acids and (pyrimidinyloxy)acetic acids were synthesized by alkylation, with methyl bromoacetate or tert-butyl bromoacetate as alkylating agents. Alkylation reaction at the nitrogen or oxygen atom for different substrates was found to be solvent dependent. N-Alkylation was favored in ethereal solvent, e.g., tetrahydrofuran and dimethoxyethane, whereas O-alkylation was predominant in dimethylformamide. These compounds were tested in vitro to determine their ability to inhibit bovine lens aldose reductase. Selected compounds were assayed in vivo, in a 4-day galactose-fed rat model. The decrease in galactitol from the control was determined in lens, nerve, and diaphragm. Several of the 6-oxopyrimidine-1-acetic acids and (pyrimidinyl-4-oxy)acetic acids were found to be potent inhibitors of bovine lens aldose reductase. A study was also undertaken to determine in vitro the transport behavior of selected compounds in the isolated rat sciatic nerve. A discussion of the structure-activity relationship of this class of compounds with reference to their intrinsic biochemical activity is reported. It is concluded, in general, that ability of a compound to penetrate the tissue membrane plays an important role in the genesis of in vivo lens aldose reductase (LAR) inhibitory activity.

  DOI：

  10.1021/jm00172a034

文献信息

• ELLINGBOE, JOHN;ALESSI, THOMAS;MILLEN, JANE;SREDY, JANET;KING, ANDREW;PRU+, J. MED. CHEM., 3,(1990) N0, C. 2892-2899
  作者：ELLINGBOE, JOHN、ALESSI, THOMAS、MILLEN, JANE、SREDY, JANET、KING, ANDREW、PRU+

  DOI：——

  日期：——
• (Pyrimidinyloxy)acetic acids and pyrimidineacetic acids as a novel class of aldose reductase inhibitors
  作者：John Ellingboe、Thomas Alessi、Jane Millen、Janet Sredy、Andrew King、Candace Prusiewicz、Frieda Guzzo、Donna VanEngen、Jehan Bagli

  DOI：10.1021/jm00172a034

  日期：1990.10

  Pyrimidineacetic acids and (pyrimidinyloxy)acetic acids were synthesized by alkylation, with methyl bromoacetate or tert-butyl bromoacetate as alkylating agents. Alkylation reaction at the nitrogen or oxygen atom for different substrates was found to be solvent dependent. N-Alkylation was favored in ethereal solvent, e.g., tetrahydrofuran and dimethoxyethane, whereas O-alkylation was predominant in dimethylformamide. These compounds were tested in vitro to determine their ability to inhibit bovine lens aldose reductase. Selected compounds were assayed in vivo, in a 4-day galactose-fed rat model. The decrease in galactitol from the control was determined in lens, nerve, and diaphragm. Several of the 6-oxopyrimidine-1-acetic acids and (pyrimidinyl-4-oxy)acetic acids were found to be potent inhibitors of bovine lens aldose reductase. A study was also undertaken to determine in vitro the transport behavior of selected compounds in the isolated rat sciatic nerve. A discussion of the structure-activity relationship of this class of compounds with reference to their intrinsic biochemical activity is reported. It is concluded, in general, that ability of a compound to penetrate the tissue membrane plays an important role in the genesis of in vivo lens aldose reductase (LAR) inhibitory activity.