4-Hydroxy tolbutamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-Hydroxy tolbutamide
• 英文别名: 1-(4-Hydroxybutyl)-3-(4-methylphenyl)sulfonylurea；1-(4-hydroxybutyl)-3-(4-methylphenyl)sulfonylurea
• 化学式: C₁₂H₁₈N₂O₄S
• 分子量: 286.352
• InChiKey: ARWJONUTYPGDMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  甲苯磺丁脲 在 liver microsomes of Caprus hircus aegagrus 、 磺胺二甲嘧啶 作用下， 以 水 为溶剂， 反应 8.0h， 生成 4-Hydroxy tolbutamide
  参考文献：
  名称：

  Differential inhibitory effects of phenytoin, diclofenac, phenylbutazone and a series of sulfonam ides on hepatic cytochrom e P4502C activityin vitro, and correlation with som e m olecular descriptors in the dwarf goat (Caprus hircus aegagrus).

  摘要：

  The aim of the present study was to investigate the potency of various sulfonamides to inhibit tolbutamide hydroxylation (a CYP2C activity) in hepatic microsomal fractions and hepatocytes of the dwarf goat. Also a number of suggested substrates for human CYP2C9 was investigated.2. From Dixon plots (microsomal fractions) if was observed that all compounds were competitive inhibitors of tolbutamide hydroxylation. Phenytoin (PT) showed the lowest K-i. K-i for the sulfonamides ranged between 205 and 4546 mu m, sulfadoxine having the lowest K-i followed by sulfadimethoxine, sulfamoxole, sulfadimidine and sulfaphenazole.3. In hepatocytes sulfaphenazole and diclofenac were the most potent inhibitors.4. Out data indicate that PT, diclofenac (DF) and phenylbutazone (PBZ) are relative strong competitive inhibitors of tolbutamide hydroxylation and they are probably also substrates for the same enzyme. Differential inhibition of tolbutamide hydroxylation by sulfonamides was observed.5. Correlation of structural parameters with the inhibition constant or the inhibition in hepatocytes showed that molecular volume, polarisability and molecular surface area are important parameters in determining the rate of inhibition of tolbutamide hydroxylation by sulfonamides in both microsomes and hepatocytes. In addition, log P-oct are also involved in determining inhibition constants in microsomal fractions.

  DOI：

  10.1080/004982597240154

文献信息

• Differential inhibitory effects of phenytoin, diclofenac, phenylbutazone and a series of sulfonam ides on hepatic cytochrom e P4502C activity<i>in vitro</i>, and correlation with som e m olecular descriptors in the dwarf goat (<i>Caprus hircus aegagrus</i>).
  作者：W. M. ZWEERS-ZEILMAKER、G. J. HORBACH、R. F. WITKAMP*

  DOI：10.1080/004982597240154

  日期：1997.1

  The aim of the present study was to investigate the potency of various sulfonamides to inhibit tolbutamide hydroxylation (a CYP2C activity) in hepatic microsomal fractions and hepatocytes of the dwarf goat. Also a number of suggested substrates for human CYP2C9 was investigated.2. From Dixon plots (microsomal fractions) if was observed that all compounds were competitive inhibitors of tolbutamide hydroxylation. Phenytoin (PT) showed the lowest K-i. K-i for the sulfonamides ranged between 205 and 4546 mu m, sulfadoxine having the lowest K-i followed by sulfadimethoxine, sulfamoxole, sulfadimidine and sulfaphenazole.3. In hepatocytes sulfaphenazole and diclofenac were the most potent inhibitors.4. Out data indicate that PT, diclofenac (DF) and phenylbutazone (PBZ) are relative strong competitive inhibitors of tolbutamide hydroxylation and they are probably also substrates for the same enzyme. Differential inhibition of tolbutamide hydroxylation by sulfonamides was observed.5. Correlation of structural parameters with the inhibition constant or the inhibition in hepatocytes showed that molecular volume, polarisability and molecular surface area are important parameters in determining the rate of inhibition of tolbutamide hydroxylation by sulfonamides in both microsomes and hepatocytes. In addition, log P-oct are also involved in determining inhibition constants in microsomal fractions.