A review of benzotriazole derivatives: versatile scaffolds for advancing therapeutics in medicinal chemistry

Benzotriazole (BtH) is recognized as a versatile heterocyclic scaffold that plays an increasingly vital role in modern drug discovery owing to its broad pharmacological potential and structural flexibility. Although BtH was first synthesized in the 19th century, recent advances in synthetic and medicinal chemistry have revitalized interest in BtH and its derivatives for developing multifunctional therapeutics. This review addresses current challenges and opportunities in BtH chemistry by integrating progress in sustainable synthesis, structure–activity relationship (SAR) analyses, and therapeutic applications. The discussion encompasses green methodologies, such as microwave-assisted, ultrasound-assisted, flow, and electrosynthesis techniques, that improve atom economy, reduce waste, and enhance energy efficiency. It also highlights how structural modifications, including halogenation, heterocyclic fusion, and metal complexation, influence biological activity and target selectivity. BtH derivatives exhibit significant antimicrobial, antiviral, anticancer, antioxidant, and enzyme-inhibitory properties, as well as other potential in neuroprotective and anti-inflammatory therapies. However, limited in vivo evaluation, lack of standardized bioassay protocols, and scalability challenges in sustainable synthesis remain key research gaps. Overall, this review synthesizes contemporary developments from 2020–2026, demonstrating that BtH serves as a privileged pharmacophore capable of engaging diverse biological targets. By consolidating mechanistic insights and eco-efficient synthesis strategies, the work provides a foundation for designing next-generation BtH-based drug candidates and advancing sustainable medicinal chemistry.