Linear triazenes: Versatile scaffolds for chemical biology and drug design

Analyzing the advances in and emergence of novel triazenes is pivotal in medicinal chemistry. Triazenes exhibit biological activity through alkylation, redox processes, or interactions with biomolecules, producing synergistic effects enabling the synthesis of derivatives with tailored pharmacokinetic profiles and enhanced activities. Although cyclic triazenes are well studied, research on linear triazenes has largely focused on their anticancer potential, leaving other therapeutic areas less explored. Given the need for chemotypes with modular synthesis and favorable pharmacology, linear triazenes warrant renewed attention. This review provides a comprehensive overview of the chemistry, biological activity, and structure-activity relationships of linear triazenes, highlighting their emerging roles in targeted therapies, fragment-based design, and bifunctional modalities, as reported since 2000.