Uses of Cyanoacetylhydrazine in Heterocyclic Synthesis Novel Synthesis of Pyrazole Derivatives with Anti-tumor Activities 英文参考文献.docVIP

Molecules 2012, 17, 8449-8463; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Uses of Cyanoacetylhydrazine in Heterocyclic Synthesis: Novel Synthesis of Pyrazole Derivatives with Anti-tumor Activities Rafat M. Mohareb 1,2,*, Nahed N. E. El-Sayed 3,4 and Mahmoud A. Abdelaziz 5,6 1 Departrment of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt 2 Department of Organic Chemistry, Faculty of Pharmacy, October University for Modern Sciences Arts (MSA), El-Wahaat Road, October City, Giza 12411, Egypt 3 National Organization for Drug Control and Research, P.O. Box 29, Cairo 11421, Egypt 4 College of Science, Department of Chemistry, King Saud University, Riyadh 11932, Saudi Arabia 5 Preparatory Year Department, AL-Ghad International Colleges for Health Sciences, Tabuk Male, Tabuk 41321, Saudi Arabia 6 Basic Science Department, Modern Academy for Engineering and Technology in Maadi, Maadi 11431, Cairo, Egypt * Author to whom correspondence should be addressed; E-Mail: raafat_mohareb@; Tel.: +20-122-3406-896. Received: 29 May 2012; in revised form: 22 June 2012 / Accepted: 26 June 2012 / Published: 12 July 2012 Abstract: The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H-pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhi