1,5-Disubstituted 1,2,3-triazoles: Molecular scaffolds for medicinal chemistry and biomolecular mimetics

Ruthenium (II) catalyzed click chemistry enable the highly efficient and selective synthesis of 1,5-disubstituted 1,2,3-triazoles. This method provides exclusive formation of the desired 1,5-regioisomer. In the past twenty years, these reactions have become a valuable tool in organic synthesis. Similar to 1,4-regioisomer of 1,2,3-triazole, 1,5-disubstituted 1,2,3-triazole functions as biocompatible linkers and biologically active scaffolds. This review focuses on the synthesis and medicinal chemistry significance of these triazoles as versatile building blocks. Notably, they serve as bioisosteres of the cis-amide bond, conferring enhanced stability and mimicking constrained amino acids, making them crucial for peptidomimetic development. Hence, we are discussing their application in the development of peptidomimetics. 1,5-Disbstituted 1,2,3- triazoles mimic cis-amide bond in the peptides, altering their conformation and biological activity. Furthermore, we have discussed its application to create novel bioactive molecules, including mimics of natural products, nucleosides, nucleotides, glycoconjugates, and protein-protein interaction inhibitors. This review highlights their substantial potential in drug discovery, and provides a valuable resource for future research in this field.