Abstract
Background: Pyridopyrimidines are of current interest because of their extensive variety of biological and pharmacological activities.
Results: A series of pyrido[2 ', 3 ': 4,5] pyrimido[2,1-b][1,3,5] thiadiazinones was obtained by aminomethylation of pyridopyrimidinethione with formaldehyde solution (37%) and different primary aromatic amines. Another series of pyrido[2 ', 3: 4,5] pyrimido[2,1-b][1,3] thiazinones was prepared by Michael addition reaction of pyridopyrimidinethione to the activated double bond of a number of arylidene malononitrile and 2-(benzo[d][1,3] dioxol-5-ylmethylene) malononitrile. The mechanisms of formation of the synthesized compounds were discussed and the assigned structure was established via microanalysis and spectral data (IR, H-1 NMR, and Ms.). A comparative study of the biological activity of the synthesized compounds with chloramphenicol and trimethoprim/sulphamethoxazole is shown in Table 1. Generally, all synthesized compounds showed adequate inhibitory effects on the growth of Gram-positive and Gramnegative bacteria.
Conclusions: In this study, we use a simple (synthetic) strategy for the synthesis of pyrimidothiadiazines, based on their aminomethylation through the Mannich reaction; they have also been synthesized by the application of the Michael addition to activated nitriles. Mechanisms and structures of the newly synthesized compounds were examined: the antimicrobial activity of some selected compounds was evaluated, which demonstrated adequate inhibitory effects.