Current Small Molecules-Based Medicinal Chemistry Approaches for Neurodegeneration Therapeutics

ChemMedChem. 2024 Feb 8:e202300705. doi: 10.1002/cmdc.202300705. Online ahead of print.ABSTRACTNeurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS) possess multifactorial aetiologies. In recent years, our understanding of the biochemical and molecular pathways across NDDs has increased, however, new advances in small molecule-based therapeutic strategies targeting NDDs are obscure and scarce. Moreover, NDDs have been studied for more than five decades, however, there is a paucity of drugs that can treat NDDs. Considering the highly complex nature of NDDs, the association of multiple risk factors, and the challenges to overcome the BBB junction, medicinal chemists have developed small organic molecule-based novel approaches to target NDDs, such as designing lipophilic molecules, applying prodrug strategies and utilizing a multitarget approach to modulate different biochemical molecular pathways involved in NDDs, in addition to, medicinal chemists making better decisions in identifying optimized drug candidates for the central nervous system (CNS) by using web-based computational tools. Further, to increase the clinical success of these drug candidates, an in vitro assay modeling the BBB has been utilized by medicinal. Herein, we examine some of the intriguing strategies taken by medicinal chemists to design small organic molecules to combat NDDs and to increase our awareness of neurodegenerative ther...
Source: ChemMedChem - Category: Chemistry Authors: Source Type: research