1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(3-hydroxy-4-nitrophenyl)ethoxy]carbonyl]hydrazine | 881404-76-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(3-hydroxy-4-nitrophenyl)ethoxy]carbonyl]hydrazine
• 英文别名: KS119OH；1-(3-hydroxy-4-nitrophenyl)ethyl N-[2-chloroethyl(methylsulfonyl)amino]-N-methylsulfonylcarbamate
• CAS: 881404-76-8
• 化学式: C₁₃H₁₈ClN₃O₉S₂
• 分子量: 459.886
• InChiKey: ICJCBDDOCRKQLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  184
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1,2-bis(methylsulfonyl)-2-(2-chloroethyl)hydrazine-carboxylic acid 1-(3-dihydrogenphosphonoxy-4-nitrophenyl)ethyl ester 在 alkaline phosphatase 作用下， 生成 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(3-hydroxy-4-nitrophenyl)ethoxy]carbonyl]hydrazine
  参考文献：
  名称：

  [EN] SULFONYL HYDRAZINES AS HYPOXIA-SELECTIVE ANTINEOPLASTIC AGENTS
  [FR] PROMEDICAMENTS D'HYDRAZINES DE SULFONYLE PORTEURS DE PHOSPHATE EN TANT QU'AGENTS ANTINEOPLASIQUES A SELECTION HYPOXIQUE

  摘要：

  公开号：

  WO2006034266A3

文献信息

• Bacterial nitroreductase enzymes and methods relating thereto
  申请人：Guise Christopher Paul

  公开号：US10357577B2

  公开（公告）日：2019-07-23

  The invention relates generally to bacterial nitroreductase enzymes and methods of use thereof: more particularly, although not exclusively, the enzymes have use in non-invasive imaging techniques, monitoring of therapeutic cell populations and gene-directed enzyme prodrug therapy. The invention also relates to the use of bacterial nitroreductase enzymes in radioimaging and/or ablation of biological agents and to compositions of use in such methods.

  本发明一般涉及细菌硝基还原酶及其使用方法：更具体地说，尽管不完全是，这种酶可用于非侵入性成像技术、治疗细胞群监测和基因导向酶原药治疗。本发明还涉及细菌硝基还原酶在放射成像和/或生物制剂消融中的应用，以及在此类方法中的使用组合物。
• 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119): a Cytotoxic Prodrug with Two Stable Conformations Differing in Biological and Physical Properties
  作者：Philip G. Penketh、Raymond P. Baumann、Krishnamurthy Shyam、Hugh S. Williamson、Kimiko Ishiguro、Rui Zhu、Emma S. E. Eriksson、Leif A. Eriksson、Alan C. Sartorelli

  DOI：10.1111/j.1747-0285.2011.01193.x

  日期：2011.10

  The anticancer prodrug 1,2‐bis(methylsulfonyl)‐1‐(2‐chloroethyl)‐2‐[[1‐(4‐nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively releases a short‐lived cytotoxin following enzymatic reduction in hypoxic environments found in solid tumors. KS119, in addition to two enantiomers, has two stable atropisomers (conformers differing in structure owing to hindered bond rotation) that interconvert at 37 °C in aqueous solution by first‐order kinetics with t1/2 values of ∼50 and ∼64 h. The atropisomers differ in physical properties such as partition coefficients that allow their chromatographic separation on non‐chiral columns. A striking difference in the rate of metabolism of the two atropisomers occurs in intact EMT6 murine mammary carcinoma cells under oxygen‐deficient conditions. A structurally related molecule, 1,2‐bis(methylsulfonyl)‐1‐(2‐chloroethyl)‐2‐[[1‐(3‐hydroxy‐4‐nitrophenyl)ethoxy]carbonyl]hydrazine (KS119WOH), was also found to exist in similar stable atropisomers. The ratio of the atropisomers of KS119 and structurally related agents has the potential to impact the bioavailability, activation, and therapeutic activity. Thus, thermally stable atropisomers/conformers in small molecules can result in chemically and enantiomerically pure compounds having differences in biological activities.
• BACTERIAL NITROREDUCTASE ENZYMES AND METHODS RELATING THERETO
  申请人：Auckland Uniservices Limited

  公开号：EP2593796A2

  公开（公告）日：2013-05-22
• US7405317B2
  申请人：——

  公开号：US7405317B2

  公开（公告）日：2008-07-29
• [EN] BACTERIAL NITROREDUCTASE ENZYMES AND METHODS RELATING THERETO<br/>[FR] ENZYMES NITRORÉDUCTASES BACTÉRIENNES ET PROCÉDÉS ASSOCIÉS
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2012008860A2

  公开（公告）日：2012-01-19

  The invention relates generally to bacterial nitroreductase enzymes and methods of use thereof: More particularly, although not exclusively, said enzymes have use in non-invasise imaging techniques, monitoring of therapeutic cell populations and gene-directed enzyme prodrug therapy. The invention also relates to the use of bacterial nitroreductase enzymes in radioimaging and/or ablation of biological agents and to compositions of use in such methods.