Review of triazole scaffolds for treatment and diagnosis of Alzheimer's disease

Triazole scaffolds, a series of 5-membered heterocycles, are well known for their high efficacy, low toxicity, and superior pharmacokinetics. Alzheimer's disease (AD) is the first neurodegenerative disorder with complex pathological mechanisms. Triazole, as an aromatic group with three nitrogen atoms, forms polar and non-polar interactions with diverse key residues in the receptor-ligand binding procedure, and has been widely used in the molecular design in the development of anti-AD agents. Moreover, considering the simple synthesis approaches, triazole scaffolds are commonly used to link two pharmacodynamic groups in one chemical molecule, forming multi-target directed ligands (MTDLs). Furthermore, the click reaction between azide- and cyano-modified enzyme and ligand provides feasibility for the new modulator discovery, compound tissue distribution evaluation, enzyme localization, and pharmacological mechanism study, promoting the diagnosis of AD course.