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.
Export Options
About this article
Cite this article as:
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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Flavonoids and Dementia: An Update
Current Medicinal Chemistry Hydrogen Sulphide and Pain
Inflammation & Allergy - Drug Targets (Discontinued) New Findings on the Neurotransmitter Modulation of Defense in the Dorsal Periaqueductal Gray
CNS & Neurological Disorders - Drug Targets Anesthetic Agents and Neuronal Autophagy. What We Know and What We Don't.
Current Medicinal Chemistry MicroRNAs in Glioblastoma: Role in Pathogenesis and Opportunities for Targeted Therapies
CNS & Neurological Disorders - Drug Targets Azathioprine in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry COVID-19: A Daily Dose of Yoga to Cope with Anxiety
Coronaviruses The Relationships between the Transforming Growth Factor-β 1, Age and the Ultrasound Parameters of Arterial Wall
Vascular Disease Prevention (Discontinued) Melatonin: Pharmacology, Functions and Therapeutic Benefits
Current Neuropharmacology Episodic Memory Dysfunction in Individuals at High-Risk of Psychosis: A Systematic Review of Neuropsychological and Neurofunctional Studies
Current Pharmaceutical Design Increased Serum Total Bile Acids can be Associated with a Small Hematoma Volume and Decreased Clinical Severity During Acute Intracerebral Hemorrhage
Current Neurovascular Research Modulating Gut Microbiota: An Emerging Approach in the Prevention and Treatment of Multiple Sclerosis
Current Neuropharmacology Editorial (Thematic Issue: Ultrasonic Vocalizations in Rats: A Tool for the Investigation of Psychoactive Drugs and Neuropsychiatric Conditions)
Current Neuropharmacology Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism
Current Drug Metabolism Bioinformatics in Biological Big Data Era
Current Bioinformatics Meet Our Associate Editor
Current Psychopharmacology Administration of a Synbiotic to Free-Living Elderly and Evaluation of Serum Cytokines. A Pilot Study
Current Pharmaceutical Design Is It the Twilight of BACE1 Inhibitors?
Current Neuropharmacology Ischemic Colitis: Current Diagnosis and Treatment
Current Drug Targets