4-amino-N-benzoyloxymethyl-N-(2-pyrimidinyl)benzenesulfonamide

• 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-amino-N-benzoyloxymethyl-N-(2-pyrimidinyl)benzenesulfonamide
• 英文别名: [(4-Aminophenyl)sulfonyl-pyrimidin-2-ylamino]methyl benzoate
• 化学式: C₁₈H₁₆N₄O₄S
• 分子量: 384.415
• InChiKey: VABXNGPYVRIKTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-N-benzoyloxymethyl-N-(2-pyrimidinyl)benzenesulfonamide 以 phosphate buffer 、 乙腈 为溶剂， 生成 4-Amino-N-hydroxymethyl-N-pyrimidin-2-yl-benzenesulfonamide
  参考文献：
  名称：

  Acyloxymethyl as a drug protecting group. Part 6

  摘要：

  Tertiary N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides were synthesised and evaluated as novel classes of potential prodrugs of agents containing a secondary sulfonamide group. The chemical and plasma hydrolyses of the title compounds were studied by HPLC, Tertiary N-acyloxymethylsulfonamides are slowly and quantitatively hydrolysed to the parent sulfonamide ill pH 7.4 phosphate buffer, with half-lives ranging from 20 h, for 7d, to 30 days, for 7g. Quantitative formation of the parent sulfonamide also occurs in human plasma, the half-lives being within 0.2-2.0 min for some substrates. The rapid rate of hydrolysis can be ascribed to plasma cholinesterase, as indicated by the complete inhibition observed at. [eserine] = 0.10 mM. These results suggest that tertiary N-acyloxymethylsulfonamides are potentially useful prodrugs for agents containing a secondary sulfonamide group, especially with pK(a) < 8, combining a high stability in aqueous media with a high rate of plasma activation. In contrast, N-[(aminocarbonyloxy)methyl]sulfonamides 7h-j do not liberate the parent sulfonamide either in aqueous buffers or in human plasma and thus appear to be unsuitable for development as sulfonamide prodrugs. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00015-8
• 作为产物：
  描述：

  苯甲酸氯甲基 、 sodium sulfadiazine 以 四氢呋喃 为溶剂， 以30%的产率得到4-amino-N-benzoyloxymethyl-N-(2-pyrimidinyl)benzenesulfonamide
  参考文献：
  名称：

  Acyloxymethyl as a drug protecting group. Part 6

  摘要：

  Tertiary N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides were synthesised and evaluated as novel classes of potential prodrugs of agents containing a secondary sulfonamide group. The chemical and plasma hydrolyses of the title compounds were studied by HPLC, Tertiary N-acyloxymethylsulfonamides are slowly and quantitatively hydrolysed to the parent sulfonamide ill pH 7.4 phosphate buffer, with half-lives ranging from 20 h, for 7d, to 30 days, for 7g. Quantitative formation of the parent sulfonamide also occurs in human plasma, the half-lives being within 0.2-2.0 min for some substrates. The rapid rate of hydrolysis can be ascribed to plasma cholinesterase, as indicated by the complete inhibition observed at. [eserine] = 0.10 mM. These results suggest that tertiary N-acyloxymethylsulfonamides are potentially useful prodrugs for agents containing a secondary sulfonamide group, especially with pK(a) < 8, combining a high stability in aqueous media with a high rate of plasma activation. In contrast, N-[(aminocarbonyloxy)methyl]sulfonamides 7h-j do not liberate the parent sulfonamide either in aqueous buffers or in human plasma and thus appear to be unsuitable for development as sulfonamide prodrugs. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00015-8

文献信息

• Acyloxymethyl as a drug protecting group. Part 6
  作者：Francisca Lopes、Rui Moreira、Jim Iley

  DOI：10.1016/s0968-0896(00)00015-8

  日期：2000.4

  Tertiary N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides were synthesised and evaluated as novel classes of potential prodrugs of agents containing a secondary sulfonamide group. The chemical and plasma hydrolyses of the title compounds were studied by HPLC, Tertiary N-acyloxymethylsulfonamides are slowly and quantitatively hydrolysed to the parent sulfonamide ill pH 7.4 phosphate buffer, with half-lives ranging from 20 h, for 7d, to 30 days, for 7g. Quantitative formation of the parent sulfonamide also occurs in human plasma, the half-lives being within 0.2-2.0 min for some substrates. The rapid rate of hydrolysis can be ascribed to plasma cholinesterase, as indicated by the complete inhibition observed at. [eserine] = 0.10 mM. These results suggest that tertiary N-acyloxymethylsulfonamides are potentially useful prodrugs for agents containing a secondary sulfonamide group, especially with pK(a) < 8, combining a high stability in aqueous media with a high rate of plasma activation. In contrast, N-[(aminocarbonyloxy)methyl]sulfonamides 7h-j do not liberate the parent sulfonamide either in aqueous buffers or in human plasma and thus appear to be unsuitable for development as sulfonamide prodrugs. (C) 2000 Elsevier Science Ltd. All rights reserved.