Abstract
In this study, a novel series of 7-substituted-[1,2,4]triazolo[4,3-f]pyrimidine derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that the compound 3i (7-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-f]pyrimidine) was among the most active agent with median effective dose (ED50) value of 34.7 mg/kg, median toxicity dose (TD50) of 262.9 mg/kg, and providing a protective index (PI=TD50 /ED50) value of 7.6. The compound 3i also showed oral activity against MES-induced seizures and lower oral neurotoxicity. The compound 3i demonstrated antagonistic activity against seizures induced by PTZ, ISN, 3-MP and thiosemicarbazide.
Keywords: Triazolo, pyrimidine, synthesis, anticonvulsant, neurotoxicity, maximal electroshock, PTZ, ISN, 3-MP, thiosemicarbazide.
Medicinal Chemistry
Title:Design, Synthesis and Anticonvulsant Activity Evaluation of 7-Substituted –[1,2,4]-Triazolo[4,3-f]Pyrimidine Derivatives
Volume: 8 Issue: 6
Author(s): Li-Ping Guan, Xin Sui, Yue Chang, Zheng-Shun Yan, Guo-Zhong Tong and You-Le Qu
Affiliation:
Keywords: Triazolo, pyrimidine, synthesis, anticonvulsant, neurotoxicity, maximal electroshock, PTZ, ISN, 3-MP, thiosemicarbazide.
Abstract: In this study, a novel series of 7-substituted-[1,2,4]triazolo[4,3-f]pyrimidine derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that the compound 3i (7-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-f]pyrimidine) was among the most active agent with median effective dose (ED50) value of 34.7 mg/kg, median toxicity dose (TD50) of 262.9 mg/kg, and providing a protective index (PI=TD50 /ED50) value of 7.6. The compound 3i also showed oral activity against MES-induced seizures and lower oral neurotoxicity. The compound 3i demonstrated antagonistic activity against seizures induced by PTZ, ISN, 3-MP and thiosemicarbazide.
Export Options
About this article
Cite this article as:
Guan Li-Ping, Sui Xin, Chang Yue, Yan Zheng-Shun, Tong Guo-Zhong and Qu You-Le, Design, Synthesis and Anticonvulsant Activity Evaluation of 7-Substituted –[1,2,4]-Triazolo[4,3-f]Pyrimidine Derivatives, Medicinal Chemistry 2012; 8 (6) . https://dx.doi.org/10.2174/1573406411208061076
DOI https://dx.doi.org/10.2174/1573406411208061076 |
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
-
Lipophilicity and Other Parameters Affecting Brain Penetration
Current Medicinal Chemistry - Central Nervous System Agents Matrix Metalloproteinase Inhibitors: New Challenges in the Era of Post Broad-Spectrum Inhibitors
Current Pharmaceutical Design PET Studies on P-Glycoprotein Function in the Blood-Brain Barrier: How it Affects Uptake and Binding of Drugs within the CNS
Current Pharmaceutical Design Valproic Acid As Anti-Cancer Drug
Current Pharmaceutical Design Relationships Between Mitochondria and Neuroinflammation: Implications for Alzheimer’s Disease
Current Topics in Medicinal Chemistry Neurological Disorders in Mice Lacking Glycogenes that are Mainly Expressed in Brain
CNS & Neurological Disorders - Drug Targets Organotypic Brain Slices of ADULT Transgenic Mice: A Tool to Study Alzheimer’s Disease
Current Alzheimer Research Cold-induced Anaphylaxis: The Case of a 9-year-old Child and Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets Psychomotor Seizure Screening and in vitro Neuroprotection Assay of Hydrazones Derived from 2-Acetyl Thiophene
Central Nervous System Agents in Medicinal Chemistry Adaptive Behavior in Williams-Beuren Syndrome, Down Syndrome, and Autism Spectrum Disorder
Current Psychiatry Reviews Nutraceuticals in Psychiatric Practice
Recent Patents on CNS Drug Discovery (Discontinued) The AMPAR Antagonist Perampanel Regulates Neuronal Necroptosis via Akt/GSK3β Signaling After Acute Traumatic Injury in Cortical Neurons
CNS & Neurological Disorders - Drug Targets An Introduction to Hardware and Methods for Biopotential Measurements: A Review
Recent Patents on Biomedical Engineering (Discontinued) PET and SPECT Radiotracers to Assess Function and Expression of ABC Transporters In Vivo
Current Drug Metabolism Pharmacogenetics and Anaesthesiology
Current Pharmacogenomics The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy
CNS & Neurological Disorders - Drug Targets Moxifloxacin Hydrochloride-Loaded Eudragit® RL 100 and Kollidon® SR Based Nanoparticles: Formulation, In vitro Characterization and Cytotoxicity
Combinatorial Chemistry & High Throughput Screening 9th International Meeting on Metabotropic Gglutamate Receptors (Taormina, Sicily, October 1-6, 2017).
Current Neuropharmacology Distinct Forms of Spinal Cysticercosis: A Vietnamese Case Series
Current Medical Imaging Non-Celiac Gluten Sensitivity Triggers Gut Dysbiosis, Neuroinflammation, Gut-Brain Axis Dysfunction, and Vulnerability for Dementia
CNS & Neurological Disorders - Drug Targets