%0 Journal Article
%T Synthesis and In Vitro Evaluation of Novel Acyclic and Cyclic Nucleoside Analogs with a Thiadiazole Ring
%A Yuxiang Zhao
%A Peter J. McCarthy
%A Cyril Párkányi
%J ISRN Organic Chemistry
%D 2013
%R 10.1155/2013/159164
%X The synthesis of six thiadiazole nucleoside analogs is reported: 5-diacetylamino-1,2,4-thiadiazol-3-one (1), 5-amino-2- (tetrahydrofuran-2-yl)-1,2,4-thiadiazol-3-one (2), 5-amino-3-[(2′-hydroxyethoxy)methyl]-1,3,4-thiadiazol-2-one (3), 5-amino-3-(4′-hydroxy-2′-hydroxymethyl-butyl)-1,3,4-thiadiazole-2-thione (4), (R)-5-amino-3-(2′,3′-dihydroxypropyl)-1,3,4-thiadiazole-2-thione (5), and (S)-5-amino-3-(2′,3′-dihydroxypropyl)-1,3,4-thiadiazole-2-thione (6). The synthesis, characterization, and properties of these new synthesized thiadiazole derivatives are discussed. A dimerization of 5-amino-3H-1,3,4-thiadiazole-2-thione (14) by sodium nitrite resulting in di-(5-amino-1,3,4-thiadiazol-2-yl) disulfide (19) is also reported. The preliminary in vitro evaluation of these newly synthesized compounds is discussed. 1. Introduction Since Heidelberger et al. discovered 5-fluorouracil, a pyrimidine antimetabolite, in 1957, pyrimidine antimetabolites have become one of the most important groups of anticancer agents. Some pyrimidine nucleosides have been proven to possess promising anticancer activity [1–8], such as Floxuridine, Cytarabine, and Gemcitabine. Many analogs of pyrimidine nucleosides are active against viruses as well. For example, Zidovudine (Azidothymidine, AZT or ZDV), Lamivudine, Idoxuridine, Trifluridine, and Cytarabine are all used for treating viral infections [9–23]. A number of these highly successful antiviral compounds are due to the collaboration between Dracinsky et al. [17] and de Clercq and Holy [17–21] (Viread, Truvada, Atripla, Lamivudine, Vistide, Hepsera). In our laboratory, we have focused on the development of novel antimetabolites for many years, including some compounds with a thiadiazole ring. Experimental evidence indicates similarities in physical and chemical properties between a –CH=CH– bond in aromatic hydrocarbons and bivalent sulfur, –S–, in sulfur heterocycles [24, 25]. For this reason, 5-amino-2H-1,2,4-thiadiazol-3-one and 5-amino-3H-1,3,4-thiadiazol-2-one can be considered as the analogs of cytosine. Based on this analogy, within the framework of our systematic studies, we have synthesized some novel acyclic or cyclic nucleoside analogs with a thiadiazole ring instead of a pyrimidine ring. 2. Results and Discussion In the present paper, we report the preparation of 5-diacetylamino-1,2,4-thioadiazol-3-one (1)？and？five thiadiazole-based？nucleoside？analogs:？5-diacetylamino-1,2,4-thiadiazol-3-one (1), 5-amino-2？(tetrahydrofuran-2-yl)-1,2,4-thiadiazol-3-one (2),
%U http://www.hindawi.com/journals/isrn.organic.chemistry/2013/159164/