CHEMICAL DESIGN AND PRECLINICAL VALIDATION OF NOVEL HETEROCYCLIC COMPOUNDS FOR PARKINSON’S DISEASE: A REVIEW OF CURRENT APPROACHES

Parkinson’s disease is a heterogeneous neurodegenerative disorder in which motor impairment coexists with non-motor symptoms, while pathological processes affect several interconnected cellular systems. This complexity complicates the development of drugs directed at a single molecular target. This review discusses key approaches to identifying novel heterocyclic compounds, including the concept of multitarget-directed ligands, the relevance of quinoline and isoquinoline scaffolds in medicinal chemistry, and principles for selecting preclinical models. Particular attention is paid to the role of computational modelling as a hypothesis-generating tool, the need to experimentally verify interactions with biological targets, and the stepwise assessment of pharmacokinetic properties, blood–brain barrier permeability, and safety. A chemically appealing structure or favourable in silico profile should not be regarded as evidence of therapeutic efficacy. The most robust strategy integrates rational molecular design with biochemical and cellular assays, complementary disease models, and stringent criteria for reproducibility.

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