Multicomponent Reactions for Multitargeted Compounds for Alzheimer`s Disease

Area of Science:

• Neuroscience
• Medicinal Chemistry
• Organic Synthesis

Background:

• Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cholinergic decline and amyloid-beta pathology.
• Multi-Target-Directed Ligands (MTDLs) represent a novel therapeutic strategy for complex diseases like AD.
• Multicomponent Reactions (MCRs) provide efficient synthesis of diverse molecular scaffolds for drug discovery.

Purpose of the Study:

• To explore the application of MCRs in synthesizing MTDLs for Alzheimer's Disease.
• To review MCRs, including Biginelli and Ugi reactions, for developing AD therapeutic agents.
• To highlight MCRs' potential in creating compound libraries targeting various AD-related pathways.

Main Methods:

• Literature review focusing on MCRs applied to Alzheimer's Disease drug discovery.
• Analysis of MTDLs developed using MCRs targeting key AD pathways.
• Discussion of specific MCRs like Biginelli and Ugi reactions in the context of AD.

Main Results:

• MCRs enable rapid and diverse synthesis of compounds with potential therapeutic value for AD.
• MTDLs developed via MCRs can simultaneously target multiple AD-related mechanisms.
• Specific MCRs have been successfully employed to generate inhibitors of AChE, BuChE, BACE1, and modulators of other AD targets.

Conclusions:

• MCRs are powerful tools for generating MTDLs and diverse compound libraries for Alzheimer's Disease research.
• The MTDL strategy, facilitated by MCRs, holds significant promise for developing novel Alzheimer's therapies.
• Further exploration of MCRs can accelerate the discovery of effective treatments for Alzheimer's Disease.