[1-methyl-5-(methylsulphinyl)-1H-imidazol-2-yl]methyl bis(2-chloroethyl)carbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [1-methyl-5-(methylsulphinyl)-1H-imidazol-2-yl]methyl bis(2-chloroethyl)carbamate
• 英文别名: 1-Methyl-2-hydroxymethyl-5-methylsulphinyl-imidazol-1H-yl N,N-bis(2-chloroethyl)carbamate；(1-methyl-5-methylsulfinylimidazol-2-yl)methyl N,N-bis(2-chloroethyl)carbamate
• 化学式: C₁₁H₁₇Cl₂N₃O₃S
• 分子量: 342.246
• InChiKey: XFVHQUWGEYDWPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  83.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-甲基-1H-咪唑-2-甲醛 在 吡啶 、 lithium aluminium tetrahydride 、 正丁基锂 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 35.25h， 生成 [1-methyl-5-(methylsulphinyl)-1H-imidazol-2-yl]methyl bis(2-chloroethyl)carbamate
  参考文献：
  名称：

  Design, Synthesis and Evaluation of Imidazolylmethyl Carbamate Prodrugs of Alkylating Agents

  摘要：

  Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2-carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)01031-5

文献信息

• Design, Synthesis and Evaluation of Imidazolylmethyl Carbamate Prodrugs of Alkylating Agents
  作者：Michael P. Hay、William R. Wilson、William A. Denny

  DOI：10.1016/s0040-4020(99)01031-5

  日期：2000.1

  Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2-carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd. All rights reserved.