3-Alkynyl Carboxamides as AEP Modulators for Treating Alzheimer's Disease

Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.

Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...

Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...