2026-06-27T15:24:48Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/924982025-09-05T17:19:36Zcom_20.500.14352_14col_20.500.14352_15

Sánchez Cebrián, Juan Domingo Alcántara León, Andrés Rafael González Matilla, Juan Francisco Sánchez Montero, José 2024-01-11T11:23:20Z 2024-01-11T11:23:20Z 2023 Sánchez, Juan D, Alcántara, Andrés R, González, Juan F, Sánchez-Montero, José María.Advances in the discovery of heterocyclic-based drugs against Alzheimer’s disease, Expert Opinion on Drug Discovery, Noviembre 2023 18:12, 1413-28, DOI: 10.1080/17460441.2023.2264766 1746-0441 10.1080/17460441.2023.2264766 https://hdl.handle.net/20.500.14352/92498 1746-045X https://doi.org/10.1080/17460441.2023.2264766 Introduction Alzheimer’s disease is a multifactorial neurodegenerative disorder characterized by beta-amyloid accumulation and tau protein hyperphosphorylation. The disease involves interconnected mechanisms, which can be clustered into two target-packs based on the affected proteins. Pack-1 focuses on beta-amyloid accumulation, oxidative stress, and metal homeostasis dysfunction, and Pack-2 involves tau protein, calcium homeostasis, and neuroinflammation. Against this background heterocyclic system, there is a powerful source of pharmacophores to develop effective small drugs to treat multifactorial diseases like Alzheimer’s. Areas covered This review highlights the most promising heterocyclic systems as potential hit candidates with multi-target capacity for the development of new drugs targeting Alzheimer’s disease. The selection of these heterocyclic systems was based on two crucial factors: their synthetic versatility and their well-documented biological properties of therapeutic potential in neurodegenerative diseases. Expert opinion The synthesis of small drugs against Alzheimer’s disease requires a multifactorial approach that targets the key pathological proteins. In this context, the utilization of heterocyclic systems, with well-established synthetic processes and facile functionalization, becomes a crucial element in the design phases. Furthermore, the selection of hit heterocyclic should be guided by a full understanding of their biological activities. Thus, the identification of promising heterocyclic scaffolds with known biological effects increases the potential to develop effective molecules against Alzheimer’s disease. eng restricted access Advances in the discovery of heterocyclic-based drugs against Alzheimer’s disease journal article