This special issue of Current Organic Chemistry is devoted to several current synthetic and biological aspects of the chemistry of diazines to illustrate the considerably increasing interest in and complexity of this research area. The wide range of the synthetic procedures and strategies recently developed and described in this issue for the syntheses of diazine derivatives may also have broader applicability in the heterocyclic chemistry, and thereby it may be useful for, and may stimulate further work in other fields of heterocyclic chemistry. I am very grateful to all authors for their efforts to contribute to this issue with highly informative and well-organized surveys. The first contribution by Baraldi et al. (University of Ferrara, Italy) describes the synthesis and medicinal chemistry of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines, and the optimization process, including structure-activity relationship analysis, to develop new selective antagonists for the A2A and A3 adenosine receptors. The study may illustrate a systematic way how to identify structural motives of complex structures which could be responsible for selective receptor-ligand interactions. In the medicinal chemistry, one of the most typical and extensively studied approaches to hit and/or lead identification is based on the syntheses of libraries of compounds with high chemical diversity. Bourguignon et al. (University Louis Pasteur, Strasbourg, France) have developed a particularly efficient pathway to the preparations of large number of polyfunctionalized pyridazines by the application of amination and palladium cross coupling reactions in tandem combination. Pyridazines containing two, three and four halogens, without or with further functional groups could be efficiently used as starting materials. Chebanov and Desenko (Institute for Scintillation Materials of National Academy of Science of Ukraine) reports on the heterocyclization reaction of unsaturated ketones with urea and structurally related derivatives to give dihydropyrimidines in good yields. Moreover, an interesting procedure with wide scope has also been developed to obtain dihydroazolopyrimidines by cyclocondensation of aminoazoles and unsaturated ketones. Pyridodiazonium systems are of interest per se representing new types of zwitterionic compounds, and as intermediates for the syntheses of otherwise hardly accessible substituted pyridines. Hajs (Chemical Research Center, Hungarian Academy of Sciences) provides a broad survey on the synthetic and theoretical aspects of the pyrido[1,2-a]pyrimidinium, pyrido[1,2- a]pyrazinium, pyrido[1,2-c]pyrimidinium, and pyrido[1,2-b]pyridazinium ring systems, and their transformations. Pyrimidine nucleosides are of great importance in the medicinal chemistry of antiviral, antibacterial and anticancer compounds. Agrofoglio (Universite d'Orlans, France) focuses particularly on the carbocyclic, acyclic, and C-5 pyrimidine nucleosides, and illustrates the recent development in the field by numerous examples. Haider (University Vienna, Austria) reviews of the medicinal chemistry of diazinocarbazoles as aza analogues of naturally occurring pyridocarbazoles, such as e.g. ellipticine, with significant anticancer activity. Some diazine analogues are bioisosters, whereas some of them are well beyond the principles of classical bioisosterism. Nevertheless, from both types there could be identified several compounds with interesting biological activities. Moreover, several elegant synthetic procedures, including Diels-Alder approach, have also been elaborated to these classes of compounds. Maes (University Antwerp) et al. extensively surveyed the most efficient methods for C- and N-functionalization of pyridazines via palladium-catalyzed cross coupling reactions including Suzuki, Stille, Sonogashira, Heck, carbonylation and Buchwald-Hartwig reactions. The review well demonstrates the wide scope of these reactions to the syntheses of a broad range of pyridazines including fused ring systems.
ASJC Scopus subject areas
- Organic Chemistry