Recent Advances in the Chemistry of 1,2,3,4-Tetrahydroisoquinoline Derivatives: Synthetic Strategies, Biological Activities, Structure-Activity Relationships, and Lead Molecules

Abstract:

1,2,3,4-Tetrahydroisoquinoline (THIQ) derivatives represent an important class of nitrogencontaining heterocycles that have attracted considerable interest owing to their structural diversity, synthetic versatility, and broad range of reported biological activities. Their structural resemblance to naturally occurring alkaloids and the ease of functionalization at different positions of the THIQ framework make them valuable scaffolds for the development of structurally diverse bioactive molecules. This review summarizes recent advances (2019-2025) in the chemistry of THIQ derivatives with particular emphasis on synthetic strategies, structural modification, representative lead molecules, and Structure-Activity Relationship (SAR) studies associated with diverse biological activities. In addition, recent developments in molecular hybridization, scaffold design, and emerging synthetic approaches for the preparation of THIQ derivatives are critically discussed. This review also highlights current research trends, key structural features governing biological performance, and future opportunities for the chemical development and functional diversification of THIQ-based scaffolds. Overall, this review provides a comprehensive resource for researchers working in heterocyclic, synthetic, and medicinal chemistry involving tetrahydroisoquinoline derivatives.