C–H Annulation in Azines to Obtain 6,5-Fused-Bicyclic Heteroaromatic Cores for Drug Discovery

Fused-bicyclic heteroaromatic cores are a common framework in drugs and other biologically active compounds. Those containing azine rings are widely used in drug discovery campaigns. Although these cores are very common, C–H functionalization of their azine moieties remains challenging, especially in annulation reactions. Therefore, this review highlights the progress made over the years in C–H annulation reactions that have produced these essential 6,5-fused bicyclic heteroaromatic cores for drug discovery. For that, the review was divided according to the five-membered rings moiety (pyrrole, pyrazole, imidazole, furan, thiophen, and thiazole) fused to different azines (pyridine, pyrazine, pyridazine, pyrimidine, and triazine). Although some important advances have been made over the years, there remains a need for research in synthetic methodology to expand the use of these heteroaromatic cores in biologically active compounds.