Thiadiazines, N,N-Heterocycles of Biological Relevance 英文参考文献.docVIP

Molecules 2012, 17, 7612-7628; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Thiadiazines, N,N-Heterocycles of Biological Relevance Hortensia Rodríguez 1,*, Margarita Suárez 2 and Fernando Albericio 1,3,4,* 1 Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, Barcelona 08028, Spain 2 Laboratory of Organic Synthesis, Department of Organic Chemistry, Faculty of Chemistry, University of Havana, Ciudad Habana 10400, Cuba; E-Mail: msuarez@fq.uh.cu 3 Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, Barcelona 08028, Spain 4 School of Chemistry, University of KwaZulu-Natal, Durban 4041, South Africa * Authors to whom correspondence should be addressed; E-Mails: hortensia.rodriguez@ (H.R.); albericio@ (F.A.). Received: 7 May 2012; in revised form: 16 June 2012 / Accepted: 19 June 2012 / Published: 25 June 2012 Abstract: The 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione scaffold has found many applications in recent years. This review is aimed at highlighting the most important aspects of these compounds: Synthesis, spectroscopic characterization and biological activities. How the chemical nature of N-substituents influences the overall activity and cytotoxicity profile will also be discussed. Keywords: heterocycles; thiadiazines; synthesis and biological activity 1. Introduction Although the first representatives of the fully saturated 3,5-dimethyltetrahydro-2H-1,3,5- thiadiazine-2-thione scaffold (Figure 1) were synthesized for the first time in 1848 [1], their correct structure was not assigned until 1944 [2]. Until the 80s, some studies addressed the synthesis [3–5] and biological applications of these derivatives [6,7].  Molecules 2012, 17 Figure 1. The 3,5-dimethyltetrahydro-2H-1,3,5-thiadiazine-2-thione scaffold. 7613 The antiprotozoal [8], antibacterial [9], antifungal [10