Tandem Synthesis of Novel thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one Derivatives and their Theoretical Pharmacokinetic Profiles

In this study, a new tandem method was developed for the synthesis of thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one derivatives. The method consists of a tandem reaction involving a subsequent formation of first the thiazole and then the triazine ring upon the addition of phenacyl bromide to a product of the condensation reaction between ethyl 2-formyl-1H-pyrrole- 1-carboxylate and thiosemicarbazide. The tandem cyclization step was completed in just 30 minutes. In order to predict the reaction mechanism, the charge densities of atoms and HOMO and LUMO energy were calculated by DFT method for the compounds obtained in the intermediate stage. In addition, a series of pyrrolotriazinone derivatives synthesized in high yields by this method were found to be suitable drug candidates according to their druglikeness and theoretical pharmacokinetic profiles.