Tetrazoles: A multi-potent motif in drug design
Ye Yuan, Muzi Li, Vasso Apostolopoulos, John Matsoukas, Wojciech M. Wolf, Mark A. T. Blaskovich, Joanna Bojarska, Zyta M. Ziora
Abstract
The unique physicochemical properties and fascinating bioisosterism of tetrazole scaffolds have received significant attention in medicinal chemistry. We report recent efforts using tetrazoles in drug design strategies in this context. Despite the increasing prevalence of tetrazoles in FDA-approved drugs for various conditions such as cancer, bacterial viral and fungal infections, asthma, hypertension, Alzheimer's disease, malaria, and tuberculosis, our understanding of their structure-activity relationships, multifunctional mechanisms, binding modes, and biochemical properties remains limited. We explore the potential of tetrazole bioisosteres in optimising lead molecules for innovative therapies, discussing applications, trends, advantages, limitations, and challenges. Additionally, we assess future research directions to drive further progress in this field.