Abstract
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
Medicinal Chemistry
Title:Structure-Based Design, Synthesis and Molecular Modeling Studies of Thiazolyl Urea Derivatives as Novel Anti-Parkinsonian Agents
Volume: 8 Issue: 6
Author(s): Faizul Azam, Medapati Vijaya Vara Prasad, Neelaveni Thangavel, Anil Kumar Shrivastava and Govind Mohan
Affiliation:
Keywords: Docking, Neuroprotection, Parkinson's disease, 1, 3-Thiazole, Urea derivatives
Abstract: 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.
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Cite this article as:
Azam Faizul, Vijaya Vara Prasad Medapati, Thangavel Neelaveni, Kumar Shrivastava Anil and Mohan Govind, Structure-Based Design, Synthesis and Molecular Modeling Studies of Thiazolyl Urea Derivatives as Novel Anti-Parkinsonian Agents, Medicinal Chemistry 2012; 8 (6) . https://dx.doi.org/10.2174/1573406411208061057
DOI https://dx.doi.org/10.2174/1573406411208061057 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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