Multifaceted Chemistry of Tetrazole. Synthesis, Uses, and Pharmaceutical Applications

Abstract

Abstract: Scientists and researchers are currently interested in the astonishing chemistry of tetrazoles due to their diverse biological applications, predominantly in the area of material and medicinal chemistry. Tetrazoles act as nonclassical bioisosteres of carboxylic acids due to their near pKa values. Tetrazole is a nitrogen-rich heterocycle possessing both electron-donating and electron-withdrawing properties. The planar structure of tetrazole favors stabilization of electrostatic repulsion of negatively charged ions by delocalization of electrons, which is advantageous for receptor–ligand interactions. Tetrazolate anions are more soluble in lipids than carboxylic acids, which allows medicine molecules to penetrate more easily through cell membranes. Tetrazoles have a wide range of biological activities, including antibacterial, antifungal, antitumor, analgesic, anti­nociceptive, antimycobacterial, antidiabetic, anticonvulsant, cyclooxygenase inhibitory, anti-inflammatory, and antihypertensive activities. The present review highlights various synthetic approaches to tetrazole derivatives by using (1) triethyl orthoformate and sodium azide, (2) alcohols and aldehydes, and (3) isocyanides. Their physical and chemical properties and applications are discussed. The review considers biological activities of tetrazoles, such as antibacterial, antifungal, analgesic, and anti-inflammatory properties, as well as their chemistry and structures. In addition, other applications, e.g., in photography, as growth hormones, and as platform for virtual screening, are discussed with concluding remarks.