Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts to discover
novel antiparkinsonian agents with improved pharmacological profile in haloperidol-induced catalepsy and oxidative
stress in mice. Furfuryl, 2- and/or 3-methoxy substituted phenyl derivatives emerged as potent agents. With exception of
2-chloro,5-trifluoromethyl substituted analog, halogen substituted derivatives exhibited moderate antiparkinsonian activity.
The results of biochemical investigations from brain homogenate of mice outline the importance of neuroprotective/
antioxidant therapy for Parkinson’s disease (PD), supporting the notion that the oxidative stress may play a significant
role in the pathophysiological mechanisms underlying PD. Molecular docking studies of these compounds with adenosine
A2A receptor exhibited very good binding interactions and warrants further studies to confirm their binding with human
A2A receptor for the design and development of potent antagonists. Parameters for Lipinski’s rule of 5 were calculated
computationally because pharmacokinetic and metabolic behaviors in the body often are linked to the physical properties
of a compound. None of the synthesized compounds violated Lipinski’s rule, making them suitable drug candidate for the
treatment of PD.
Keywords: Docking, Neuroprotection, Parkinson's disease, 1, 3-Thiazole, Urea derivatives
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