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
-
Ag/CdS Nanocomposite: An Efficient Recyclable Catalyst for the Synthesis of Novel 8-Aryl-8H-[1,3]dioxolo[4,5-g]chromene-6-carboxylic Acids under Mild Reaction Conditions
Combinatorial Chemistry & High Throughput Screening Recent Applications of Nanomaterials Based on Electrochemical Drug Analysis
Current Analytical Chemistry Ethanol Withdrawal and Hyperalgesia
Current Drug Abuse Reviews Atrial Fibrillation in Patients Undergoing Surgical Revascularization: An Update on Pharmacologic Prophylaxis
Cardiovascular & Hematological Agents in Medicinal Chemistry Gemcitabine-Related Atrial Fibrillation: A Case Report and Review of the Literature
Current Drug Safety Insulin and Endothelial Function: Physiological Environment Defines Effect on Atherosclerotic Risk
Current Diabetes Reviews Three Decades of P-gp Inhibitors: Skimming Through Several Generations and Scaffolds
Current Medicinal Chemistry Effect of Hemodialysis on Pharmacokinetics of Ezogabine/Retigabine and its N-Acetyl Metabolite in Patients with End Stage Renal Disease
Current Clinical Pharmacology Blood Pressure Lowering and Outcomes in type 2 Diabetes: Implications of the Blood Pressure-Lowering Arm of the Advance Trial
Current Hypertension Reviews Whole Milk and Full-Fat Dairy Products and Hypertensive Risks
Current Hypertension Reviews Prevention and Treatment for Chemotherapy-Induced Peripheral Neuropathy: Therapies Based on CIPN Mechanisms
Current Neuropharmacology Continuous Infusion of Antibiotics in Critically Ill Patients
Current Clinical Pharmacology COX-Inhibiting Nitric Oxide Donors (CINODs): Potential Benefits on Cardiovascular and Renal Function
Cardiovascular & Hematological Agents in Medicinal Chemistry Why and How We Should Treat Elderly Patients with Hypertension?
Current Vascular Pharmacology Analgesic Considerations for Liver Transplantation Patients
Current Clinical Pharmacology Methylene Blue and Vasoplegia: Who, When, and How?
Mini-Reviews in Medicinal Chemistry Levosimendan: A Novel Agent in Heart Failure
Recent Patents on Cardiovascular Drug Discovery GABAB Receptors as Potential Therapeutic Targets
Current Drug Targets - CNS & Neurological Disorders Natural Fused Heterocyclic Flavonoids: Potent Candidates as Anti- Inflammatory and Anti-Allergic Agents in the Treatment of Asthma
Current Bioactive Compounds A Comprehensive Review on Phytochemistry and Pharmacological Effects of Stinging Nettle (Urtica dioica)
Current Traditional Medicine