Synthesis and Antitumor Activity of New 1,2,4-Triazine and [1,2,4]Triazolo[4,3-b][1,2,4]triazine Derivatives and Their Thioglycoside and Acyclic C-Nucleoside Analogs Wael A. El-Sayed, a * Ibrahim F. Nassar, b and Adel A.-H. Abdel-Rahman c * a Department of Photochemistry, National Research Centre, Cairo, Egypt b Faculty of Education, Ain Shams University, Abbassia, Cairo, Egypt c Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt *E-mail: adelnassar63@hotmail.com (or) waelshendy@gmail.com DOI 10.1002/jhet.522 Published online 10 September 2010 in Wiley Online Library (wileyonlinelibrary.com). New 1,2,4-triazine and their derived 1,2,4-triazolo[3,4-b][1,2,4]triazine derivatives were synthesized starting from 5,6-diphenyl-1,2,4-triazine-3-thiol. Furthermore, the corresponding 1,2,4-triazolo[3,4-b] [1,2,4]-triazine thioglycosides and acyclic C-nucleoside analogs were synthesized. The newly synthe- sized compounds were evaluated for their antitumor activity and some of them showed high inhibition activities. J. Heterocyclic Chem., 48, 135 (2011). INTRODUCTION 1,2,4-Triazines and their condensed derivatives occupy a pivotal position in modern medicinal chemis- try, because of their high potential biological activities. The 1,2,4-triazine ring is a prominent structural motif found in numerous natural and synthetic biologically active compounds. For example, the well-known antivi- ral drug azaribine is structurally based on the 1,2,4-tria- zine scaffold [1]. In addition, certain azanucleosides, for example, 6-azacytosine and 6-azauracil, bearing the 1,2,4-triazine heterocycle, have displayed an impressive array of biological activities, among which antiviral [2,3] and antitumor [4,5] activities. Condensed 1,2,4-tri- azines found various applications as pharmaceuticals, herbicides, pesticides, and dyes [6,7]. They showed an interesting broad spectrum of antiproliferative activity and a pronounced growth inhibitory activity against leu- kemic cell lines and a wide range of cancer cells [8,9] revealing in vitro antitumor and antifungal activities [10,11]. It is noteworthy that many potential antiviral and anticancer drugs have been modeled on them [12,13]. 1,2,4-Triazine derivatives are known to possess antitubercular, antibacterial, fungicidal, insecticidal, herbicides hypotensive, and hypothermic activities [6,14–17]. Many 1,2,4-triazines have been screened in vitro supporting their anti-HIV and anti-cancer activ- ities [18,19]. On the other hand, the glycosylthio hetero- cycles [20–23] and the acyclic nucleoside analogs with modification of both the glycon part and the heterocyclic base have stimulated extensive research as biological V C 2010 HeteroCorporation January 2011 135