Abstract
This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α1-adrenoceptors, with exception of 6d, and are selective over α2 receptor. The most potent compound 5f displayed 62-fold α2/α1 selectivity with Ki value of 27.3 nM for α1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α1-adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α-adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.
Keywords: α-adrenoceptor ligands, N-arylpiperazine derivatives, lipophilicity, pyridine, 2-pyridone.
Medicinal Chemistry
Title:Studies on Novel Pyridine and 2-pyridone Derivatives of N-arylpiperazine as α-adrenoceptor Ligands
Volume: 10 Issue: 2
Author(s): Marzena Baran, Elzbieta Kepczynska, Marek Zylewski, Agata Siwek, Marek Bednarski and Marek Tadeusz Cegla
Affiliation:
Keywords: α-adrenoceptor ligands, N-arylpiperazine derivatives, lipophilicity, pyridine, 2-pyridone.
Abstract: This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α1-adrenoceptors, with exception of 6d, and are selective over α2 receptor. The most potent compound 5f displayed 62-fold α2/α1 selectivity with Ki value of 27.3 nM for α1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α1-adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α-adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.
Export Options
About this article
Cite this article as:
Baran Marzena, Kepczynska Elzbieta, Zylewski Marek, Siwek Agata, Bednarski Marek and Cegla Tadeusz Marek, Studies on Novel Pyridine and 2-pyridone Derivatives of N-arylpiperazine as α-adrenoceptor Ligands, Medicinal Chemistry 2014; 10 (2) . https://dx.doi.org/10.2174/0929867320999131122114922
DOI https://dx.doi.org/10.2174/0929867320999131122114922 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
Related Articles
-
Phytochemical and Pharmacological Activity Profile of Crataegus oxyacantha L. (Hawthorn) - A Cardiotonic Herb
Current Medicinal Chemistry Closed-loop Neuropharmacology for Epilepsy: Distant Dream or Future Reality?
Current Neuropharmacology Structure-Function Relationships of PEDF
Current Molecular Medicine Thrombocytopenia in HIV Disease: Clinical Relevance, Physiopathology and Management
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Antineovascular Agents in the Treatment of Eye Diseases
Current Pharmaceutical Design Beta-Blockers in Pediatric Hypertrophic Cardiomyopathies
Reviews on Recent Clinical Trials Endothelin-1 Actions on Vascular Smooth Muscle Cell Functions As a Target for the Prevention of Atherosclerosis
Current Vascular Pharmacology Recent Advances in the Management of Pulmonary Arterial Hypertension
Current Respiratory Medicine Reviews Pharmacology and Therapeutic Potential of Sigma1 Receptor Ligands
Current Neuropharmacology Calcitonin Gene-Related Family Peptides in Vascular Adaptations, Uteroplacental Circulation, and Fetal Growth
Current Vascular Pharmacology Drug Therapy of Neuropathic Pain: Current Developments and Future Perspectives
Current Drug Targets Proteases and their Receptors as Mediators of Inflammation-Associated Colon Cancer
Current Pharmaceutical Design Genetics and Personalized Medicine in Antidepressant Treatment
Current Pharmaceutical Design Circulatory Syndrome: An Evolution of the Metabolic Syndrome Concept!
Current Cardiology Reviews Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches
Current Cancer Drug Targets Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review
Current Topics in Medicinal Chemistry Medical Complications in Anorexia and Bulimia Nervosa
Endocrine, Metabolic & Immune Disorders - Drug Targets Functional Signaling Biases in G Protein-Coupled Receptors: Game Theory and Receptor Dynamics
Mini-Reviews in Medicinal Chemistry Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Meet Our Associate Editor
Current Molecular Medicine