Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application

Triazole demonstrates distinctive physicochemical properties, characterized by weak basicity, various dipole moments, and significant dual hydrogen bond acceptor and donor capabilities. These features are poised to play a pivotal role in drug–target interactions. The inherent polarity of triazole contributes to its lower logP, suggesting the potential improvement in water solubility. The metabolic stability of triazole adds additional value to drug discovery. Moreover, the metal-binding capacity of the nitrogen atom lone pair electrons of triazole has broad applications in the development of metal chelators and antifungal agents. This Perspective aims to underscore the unique physicochemical attributes of triazole and its application. A comparative analysis involving triazole isomers and other heterocycles provides guiding insights for the subsequent design of triazoles, with the hope of offering valuable considerations for designing other heterocycles in medicinal chemistry.