Rational design of hybrid thienopyrimidine derivatives as potential modulators of neurodegeneration

Abstract

Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and other forms of cognitive decline represent one of the most significant medical and social challenges of modern healthcare. Their pathogenesis is multifactorial, involving disturbances in cholinergic and glutamatergic neurotransmission, oxidative stress, neuroinflammation, imbalance of neurotransmitter systems, and the accumulation of pathological protein aggregates. This complexity of biological mechanisms makes it impossible to effectively modify the course of neurodegeneration using drugs with narrowly targeted mechanisms of action. Current therapeutic approaches provide only symptomatic relief and do not influence the key pathways driving disease progression. This underscores the need to develop new chemical platforms and molecular architectures capable of simultaneously modulating several pathogenetically relevant targets. In this context, multitarget hybrid molecules that combine pharmacophoric elements of different origins are considered a promising direction in medicinal chemistry.