Benzene fused pyrimidine-based derivatives and their biological properties

Benzene fused pyrimidine (quinazoline) is widely utilized as a bioactive scaffold during the development of drugs for a multitude of disease states. The quinazoline scaffold has enjoyed routine use in the design of kinase inhibitors because of its adaptability to selectively engage a desired ATP-binding pocket. The medicinal chemistry applications of the quinazoline scaffold have expanded to include drugging cellular surface proteins including Toll like receptor 7/8, IKur, and P-glycoprotein, as well as intracellular nonkinase targets such as tubulin. The spatial orientation of the quinazoline core while bound to ATP-binding pockets has permitted the successful bifunctionalization through substitution of positions 6 and 7. The two nitrogens present in the quinazoline scaffold prove useful for improving drug solubility, drug-like properties, and commonly engage the target protein via hydrogen bonding interactions. This chapter highlights the medicinal chemistry efforts, biological activities, and syntheses of selected pipeline quinazoline compounds reported during the years 2015–21.