Full-Text Search:
Home|Journal Papers|About CNKI|User Service|FAQ|Contact Us|中文
《Acta Chimica Sinica》 1959-06
Add to Favorite Get Latest Update

TUMOUR CHEMOTHERAPY——Ⅱ.NITROGEN MUSTARDS RELATED TO LOCAL ANESTHETICS,PROCAINE,PERCAINE AND OTHERS

PAN PEI-CHAUN JEN YUN-FENG WANG YUEN-YIN KAO YEE-SHENG (Institute of Materia Medica,Academia Sinica,Shanghai)  
The preparation of two kinds of nitrogen mustards related to local anesthetics wasdescribed.The compounds were(1).β-diethyl-amino-ethyl-ρ-bis-(2-chloroethyl)aminobenzoate(Ⅳ,procaine-mustard),in which the ρ-amino-group of procaine(Ⅱ)wasreplaced by bis-(2-chloroethyl)amino group(Ⅰ).Similarly,nitrogen mustards Ⅴ,Ⅶ,Ⅷ,Ⅸa.Ⅸb and Ⅸc related to thiocaine and other anesthetics have also been prepared.(2).N-β-diethylamino-ethyl 2-n-butoxy-6-bis-(2-chloroethyl)amino-cinchoninic acid amide(ⅩⅥ,percaine-mustard),which was obtained by introducing Ⅰ to the molecule of percaine(ⅩⅢ).By doing so,the authors are in the hope to obtain a drug which,when applingdirectly to tumour tissue will not only act locally so as to prevent the normal tissue frombeing poisoned but will exert also the pain-relieving action.Compound Ⅳ was obtained by the following ways:(1)Ⅱ was condensed withethylene oxide to give ρ-bis(2-hydroxyethyl)amino-compound(Ⅲ),which was then treatedwith thionyl chloride to form Ⅳ.(2).ρ-bis(2-chloroethyl)amino-benzoyl chloride(Ⅵ)was reacted directly with diethylamnio-ethanol.Compounds Ⅴ,Ⅶ,Ⅷ and Ⅸa(or Ⅸb or Ⅸc)were obtained by treatment of Ⅵwith dimethylamino-ethanol,diethylamino-ethyl mercaptan,diethylaminoethyl-amine,andn-propanol(or n-butanol or iso-pentanol)respectively.The compound ⅩⅥ was prepared by a 5-step synthesis starting from 2-chloro-6-nitro-cinchoninic acid chloride(Ⅹ)which was treated with diethylamine to form N-β-diethyl-amino-ethyl 2-chloro-6-nitro cinchoninic acid amide(Ⅺ).The latter was then converted toN-β-diethylamino-ethyl 2-n-butoxy-6-nitrocinchoninic acid amide(Ⅻ)by treating with sodiumhutoxylate.By direct nitration of percaine(ⅩⅢ)there was also formed Ⅻ,which uponcatalytic hydrogenation led to the formation of the corresponding 6-amino-compound(ⅩⅣ).The latter,on treatment with ethylene oxide,gave 6-his(2-chloroethyl)amino compond(ⅩⅤ)Which formed the desired product ⅩⅥ after being reacted with phosphorus oxychlo-ride.Compound Ⅻ exhibited quite strong local anesthetic activity;procaine-mustard Ⅳand percaine-mustard ⅩⅥ still retain the local anesthetic action as the parent compounds,but the corresponding bis(2-hydroxyethyl)amino compounds Ⅲ and ⅩⅤ were inactive.Compounds Ⅳ,Ⅴ,Ⅶ,Ⅷ and ⅩⅥ were active in vitro against tumour cells,S.180and Ehrlich ascites tumour.Pharmacological examinations are in progress.
Download(CAJ format) Download(PDF format)
CAJViewer7.0 supports all the CNKI file formats; AdobeReader only supports the PDF format.
【Secondary References】
Chinese Journal Full-text Database 8 Hits
1 LIANG Pei,QIN Yong chao,JIANG Zu cheng and XIONG Chao mei (College of Chemistry and Environmental Science,Wuhan University,Wuhan 430072),Fenxi Shiyanshi,2000,19(3):56~59;Separation and Determination of Four Fluoroquinolone Antibiotics by RP HPLC[J];ANALYTICAL LABORATORY;2000-03
2 Wang Bin ,Wang Jiesheng,Liang Yanyu (Department of Development,Kunshan Double Crane Pharmaceutical Co.Ltd.,Kunshan 215315),Huaxue Shiji,2001,23(4),243;245;Synthesis of 2-acetonyloxo-3,4-difluoro-nitrobenzene[J];Chemical Reagents;2001-04
3 SUN Hui1, DONG Xiangchao1, L Xianyu2, WANG Haibo1, HAN Jianfang1 (1. Department of Chemistry, Nankai University, Tianjin 300071, China; 2. College of Life Science, Nankai University, Tianjin 300071, China);Separation and Determination of Fluoroquinolones with a Molecularly Imprinted Polymer[J];Chinese Journal of Chromatography;2003-03
4 ZHANG Yi,DONG Xiang-chao (College of Chemistry,Nankai University,Tianjin 300071,China);Evaluation of Enrofloxacin Imprinted Polymeric Microspheres Synthesized with Living/Controlled Radical Polymerization[J];Journal of Instrumental Analysis;2008-10
5 Yang Yushe(Yang YS), Ji Ruyun(Ji RY), Chen Kaixian(Chen KX) and Ding Jian(Ding J) (Shanghai Institute of Materia Medica, Shanghai 200031);STUDIES ON SYNTHESIS ANTIBACTERIAL AND ANTITUMOR ACTIVITY OF (S) (-) OFLOXACIN ANALOGUES[J];ACTA PHARMACEUTICA SINICA;1999-02
6 HU Wei-xiao,SUN Nan,YANG Zhong-yu (Institute of Pharmaceutical Engineering,Zhejiang University of Technology,Hangzhou 310032,China);A Study on Synthesis and Anticancer Activity of Thiosemicarbazones[J];Chinese Journal of Medicinal Chemistry;2001-03
7 TIAN Meng chao,QU Ling bo,XIE Jian gang,CHEN Rong feng (Department of Chemistry,Zhengzhou University,Zhengzhou 450052,China);Syntheses and antibacterial activity of 1-alkyl-6-fluoro-7-(4-acyl-1-piperazinyl)-1,4-dihydro-4-oxo- quinoline-3-carboxylic acid and its derivatives[J];Chinese Journal of Medicinal Chemistry;2002-05
8 LI Mei, QI JianJuna, GUO HuiYuana (Centre for Drug Evaluation, Ministry of Public Health, Beijing 100050;a Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050);RECENT PROGRESS OF RESEARCH AND DEVELOPMENT OF QUINOLONE ANTIBACTERIAL AGENTS IN CHINA[J];CHINESE JOURNAL OF PHARMACEUTICALS;1999-06
©2006 Tsinghua Tongfang Knowledge Network Technology Co., Ltd.(Beijing)(TTKN) All rights reserved