N-(2-chloroethyl)-2-methyl-1,2-bis(methylsulfonyl)hydrazinecarboxamide | 187481-82-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: N-(2-chloroethyl)-2-methyl-1,2-bis(methylsulfonyl)hydrazinecarboxamide
• CAS: 187481-82-9
• 化学式: C₆H₁₄ClN₃O₅S₂
• 分子量: 307.779
• InChiKey: KVXOHAWRUKJUPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.0
• 重原子数：
  17.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  103.86
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(2-chloroethyl)-2-methyl-1,2-bis(methylsulfonyl)hydrazinecarboxamide 在 吡啶 、 nitrosonium tetrafluoroborate 作用下， 以 乙腈 为溶剂， 反应 2.5h， 生成 N-(2-chloroethyl)-2-methyl-1,2-bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide
  参考文献：
  名称：

  Chloroethylating and methylating dual function antineoplastic agents display superior cytotoxicity against repair proficient tumor cells

  摘要：

  Two new agents based upon the structure of the clinically active prodrug laromustine were synthesized. These agents, 2-(2-chloroethyl)-N-methyl-1,2-bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide (1) and N-(2-chloroethyl)-2-methyl-1,2-bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide (2), were designed to retain the potent chloroethylating and DNA cross-linking functions of laromustine, and gain the ability to methylate DNA at the O-6 position of guanine, while lacking the carbamoylating activity of laromustine. The methylating arm was introduced with the intent of depleting the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT). Compound 1 is markedly more cytotoxic than laromustine in both AGT minus EMT6 mouse mammary carcinoma cells and high AGT expressing DU145 human prostate carcinoma cells. DNA cross-linking studies indicated that its cross-linking efficiency is nearly identical to its predicted active decomposition product, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl) hydrazine (90CE), which is also produced by laromustine. AGT ablation studies in DU145 cells demonstrated that 1 can efficiently deplete AGT. Studies assaying methanol and 2-chloroethanol production as a consequence of the methylation and chloroethylation of water by 1 and 2 confirmed their ability to function as methylating and chloroethylating agents and provided insights into the superior activity of 1. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.016