Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder mainly characterized by a progressive neurodegeneration of the dopaminergic neurons. The available pharmacological therapy for PD aims to stop the progress of symptoms, reduce disability, slowing the neurodegenerative process and/or preventing long-term complications along the therapy. The main strategic developments that have led to progress in the medical management of PD have focused on improvements in dopaminergic therapies. Despite all the recent research, there are only a few classes of drugs approved for the treatment of motor related symptoms of PD which primarily act on the dopaminergic neurons system: L-dopa, dopamine agonists, monoamine oxidase-B (MAO-B) and catechol-O-methyl transferase (COMT) inhibitors. Anticholinergic drugs and glutamate antagonists are also available but are not commonly used in routine practice. As no effective therapeutic strategy has yet been attended, other solutions must be investigated. Privileged structures, such as indoles, arylpiperazines, biphenyls and benzopyranes are currently ascribed as helpful approaches. Different families of nitrogen and oxygen heterocycles, such as pyrazoles, hydrazinylthiazoles, xanthones, coumarins or chromones have also been extensively used as scaffolds in medicinal chemistry programs for searching novel MAO-B inhibitors. Nitrogen derivatives play a key role in this subject with several studies pointing out hydrazines, thiazoles or indoles as important scaffolds for the development of novel MAO-B inhibitors. This review comprises an overview of the state of the art on the actual pharmacological therapy for PD followed by a specific focus on the discovery and development of nitrogen-based heterocyclic compounds analogues as promising MAO-B inhibitors.
Keywords: Hydrazinylthiazoles, indoles, isatins and phthalimides, MAO-B inhibitors, nitrogen heterocycles, Parkinson’s disease and therapy, pyridazine, pyrimidine and pyrazole derivatives, quinazolinones
Current Topics in Medicinal Chemistry
Title:Parkinson's Disease Management. Part II- Discovery of MAO-B Inhibitors Based on Nitrogen Heterocycles and Analogues
Volume: 12 Issue: 20
Author(s): Joana Reis, Igor Encarnacao, Alexandra Gaspar, Aliuska Morales, Nuno Milhazes and Fernanda Borges
Affiliation:
Keywords: Hydrazinylthiazoles, indoles, isatins and phthalimides, MAO-B inhibitors, nitrogen heterocycles, Parkinson’s disease and therapy, pyridazine, pyrimidine and pyrazole derivatives, quinazolinones
Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder mainly characterized by a progressive neurodegeneration of the dopaminergic neurons. The available pharmacological therapy for PD aims to stop the progress of symptoms, reduce disability, slowing the neurodegenerative process and/or preventing long-term complications along the therapy. The main strategic developments that have led to progress in the medical management of PD have focused on improvements in dopaminergic therapies. Despite all the recent research, there are only a few classes of drugs approved for the treatment of motor related symptoms of PD which primarily act on the dopaminergic neurons system: L-dopa, dopamine agonists, monoamine oxidase-B (MAO-B) and catechol-O-methyl transferase (COMT) inhibitors. Anticholinergic drugs and glutamate antagonists are also available but are not commonly used in routine practice. As no effective therapeutic strategy has yet been attended, other solutions must be investigated. Privileged structures, such as indoles, arylpiperazines, biphenyls and benzopyranes are currently ascribed as helpful approaches. Different families of nitrogen and oxygen heterocycles, such as pyrazoles, hydrazinylthiazoles, xanthones, coumarins or chromones have also been extensively used as scaffolds in medicinal chemistry programs for searching novel MAO-B inhibitors. Nitrogen derivatives play a key role in this subject with several studies pointing out hydrazines, thiazoles or indoles as important scaffolds for the development of novel MAO-B inhibitors. This review comprises an overview of the state of the art on the actual pharmacological therapy for PD followed by a specific focus on the discovery and development of nitrogen-based heterocyclic compounds analogues as promising MAO-B inhibitors.
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Reis Joana, Encarnacao Igor, Gaspar Alexandra, Morales Aliuska, Milhazes Nuno and Borges Fernanda, Parkinson's Disease Management. Part II- Discovery of MAO-B Inhibitors Based on Nitrogen Heterocycles and Analogues, Current Topics in Medicinal Chemistry 2012; 12 (20) . https://dx.doi.org/10.2174/1568026611212200002
DOI https://dx.doi.org/10.2174/1568026611212200002 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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