Recent Advances in the Development of Nitrogen-containing Heterocyclic Anti-alzheimer's Agents

Alzheimer's disease (AD) remains one of the major neurodegenerative diseases overwhelming the world today. Alzheimer's is the most complicated as well as perplexing disease encountering serious global health issues. Alzheimer's disease is well characterized as a general cause of dementia, which includes issues with memory, language, problem-solving, and other cognitive behaviours, such as disabled perception as well as trouble talking due to degeneration of neurons. According to the latest report, there are about 44 million individuals who are currently suffering from dementia, which has been prophesied to extensively grow up to 3-fold by 2050. Alzheimer's disease is usually triggered by numerous associated factors, including depleted amount of acetylcholine (ACh), excessive aggregation of β-amyloid peptide (Aβ), tau hyperphosphorylation with neurofibrillary tangle formation as well as deposition of feeble plaques in a specific portion of the brain (hippocampus and cortex). Besides these superior factors, sometimes AD can be induced or become complex due to several reasons, such as inflammatory mechanisms and oxidative stress. Furthermore, heterocyclic scaffolds comprise assorted implications in the drug design and development process. Heterocycles have also elicited their evolving role as core scaffolds in numerous synthetic derivatives with potent anti-Alzheimer's potential. There are only limited drugs that are present in the market to treat Alzheimer's disease in an efficacious manner. Hence, the identification, design, and development of new anti-Alzheimer's drugs are an emerging need to eradicate complex clinical indications associated with Alzheimer's disease. This review aims to summarize various recent advancements in the medicinal chemistry of heterocycle-based compounds with the following objectives: (1) to represent inclusive literature reports describing the anti-Alzheimer's potential of heterocyclic derivatives; (2) to cast light on recent advancements in the medicinal chemistry of heterocyclic compounds endowed with therapeutic potential against Alzheimer's disease; (3) to summarize the comprehensive correlation of structure-activity relationship (SAR) with the pharmacological responses, including in silico and mechanistic studies to provide ideas related to design and development of lead molecules.