Parkinson¿s disease (PD) is a neurodegenerative, hereditary/sporadic condition characterized by progressive and debilitating nervous system dysfunction (altered movement and cognitive impairment). The loss of dopaminergic neurons and the deficiency of dopamine, in the nigrostriatal pathway (Substantia Nigra pars compacta) is the main hallmark feature in PD. Current therapeutic management of PD largely involves strategies to optimize the replacement of deficient dopamine, using dopamine agonists and inhibitors of dopamine-metabolizing enzymes (i.e. hMAO-B). But these treatments are unlikely to be curative or effective alone. In this kind of multifactorial pathologies, drugs are strongly required to address the varied pathological aspects focusing a combine pharmacological activity on a single molecular entity. As a matter of this, a promising approach results from multifunctional compounds that display the ability to simultaneously interact with alternative targets. Due to the importance of selective hMAO-B inhibitors and A2A receptor antagonists in the treatment of PD, our aim is to design novel compounds endowed with these dual pharmacological activities. The choice of thiazole derivatives as the scaffold to be studied is corroborated by structure-activity relationships on this topic and data reported in the literature. Each compound will be purified and fully characterized before the biological evaluation by means of spectroscopic methods and elemental analysis to verify purity and stability. The diastereoisomers will be separate using chiral phases on HPLC system.
