Tetrazole
derivatives are a prime class of heterocycles, very important to medicinal
chemistry and drug design due to not only their bioisosterism to carboxylic
acid and amide moieties but also to their metabolic stability and
other beneficial physicochemical properties. Although more than 20
FDA-approved drugs contain 1H- or 2H-tetrazole substituents, their exact binding mode, structural biology,
3D conformations, and in general their chemical behavior is not fully
understood. Importantly, multicomponent reaction (MCR) chemistry offers
convergent access to multiple tetrazole scaffolds providing the three
important elements of novelty, diversity, and complexity, yet MCR
pathways to tetrazoles are far from completely explored. Here, we
review the use of multicomponent reactions for the preparation of
substituted tetrazole derivatives. We highlight specific applications
and general trends holding therein and discuss synthetic approaches
and their value by analyzing scope and limitations, and also enlighten
their receptor binding mode. Finally, we estimated the prospects of
further research in this field.