Abstract
Several N-hydroxyalkyl desloratadines and N-methoxyl ethyl desloratadine were prepared and evaluated for H1 antihistamine activity. The effects on isolated ileum smooth muscle tension in guinea pigs in vitro and asthma-relieving effects on the histamine-induced asthmatic reaction in guinea-pigs in vivo were examined. Most of them exhibited satisfactory H1 antihistamine activity and were obviously more potent than loratadine. Among these, Compound 3, N-(3- hydroxy)propyl desloratadine was the most active one. And it was chosen as a candidate for evaluation of acute toxicity (LD50= 0.876(0.784-0.980) g/kg), significantly superior to that of desloratadine (LD50=0.353 g/kg). Meanwhile, the experimental results demonstrated that the oxygen atom in the side carbon chain is crucial for enhancing the antihistamine activities.
Keywords: Acute toxicity, Antiallergic activity, Antihistamine, Asthma-relieving effect, Desloratadine analogues, Ileum contraction effect
Medicinal Chemistry
Title:Design, Synthesis and Antihistamine Evaluations of Several N-hydroxyalkyl Desloratadine Analogues
Volume: 8 Issue: 6
Author(s): Yan Lin, Yue Wang, Li-feng Sima, Dong-hua Wang, Li-gong Chen and Lei Li
Affiliation:
Keywords: Acute toxicity, Antiallergic activity, Antihistamine, Asthma-relieving effect, Desloratadine analogues, Ileum contraction effect
Abstract: Several N-hydroxyalkyl desloratadines and N-methoxyl ethyl desloratadine were prepared and evaluated for H1 antihistamine activity. The effects on isolated ileum smooth muscle tension in guinea pigs in vitro and asthma-relieving effects on the histamine-induced asthmatic reaction in guinea-pigs in vivo were examined. Most of them exhibited satisfactory H1 antihistamine activity and were obviously more potent than loratadine. Among these, Compound 3, N-(3- hydroxy)propyl desloratadine was the most active one. And it was chosen as a candidate for evaluation of acute toxicity (LD50= 0.876(0.784-0.980) g/kg), significantly superior to that of desloratadine (LD50=0.353 g/kg). Meanwhile, the experimental results demonstrated that the oxygen atom in the side carbon chain is crucial for enhancing the antihistamine activities.
Export Options
About this article
Cite this article as:
Lin Yan, Wang Yue, Sima Li-feng, Wang Dong-hua, Chen Li-gong and Li Lei, Design, Synthesis and Antihistamine Evaluations of Several N-hydroxyalkyl Desloratadine Analogues, Medicinal Chemistry 2012; 8 (6) . https://dx.doi.org/10.2174/1573406411208061126
DOI https://dx.doi.org/10.2174/1573406411208061126 |
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
-
Purine Derivatives as Ligands for A3 Adenosine Receptors
Current Topics in Medicinal Chemistry Proresolution Mediators and Receptors: Novel Drug Targets for Enhancing Pharmacological Armamentarium against Periodontal Inflammation
Infectious Disorders - Drug Targets Synthesis of Pyrimidine-Annulated Five-Membered Heterocycles: An Overview
Current Organic Chemistry Bacterial Proteases in Disease – Role in Intracellular Survival, Evasion of Coagulation/ Fibrinolysis Innate Defenses, Toxicoses and Viral Infections
Current Pharmaceutical Design Various Non-Injectable Delivery Systems for the Treatment of Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Inhibition of Drug Efflux in Mycobacteria with Phenothiazines and Other Putative Efflux Inhibitors
Recent Patents on Anti-Infective Drug Discovery Refractory Cough as a Remote Manifestation of Retroperitoneal Liposarcoma
Current Cancer Therapy Reviews Neuromodulatory and Anti-Inflammatory Ingredient for Sensitive Skin: In Vitro Assessment
Inflammation & Allergy - Drug Targets (Discontinued) Natural Antioxidants: Therapeutic Prospects for Cancer and Neurological Diseases
Mini-Reviews in Medicinal Chemistry T Cell Targeted Strategies for Improved Efficacy and Safety of Specific Immunotherapy for Allergic Disease
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Therapeutic Potential of microRNA Against Th2-associated Immune Disorders
Current Topics in Medicinal Chemistry Dibenzoylmethane Activates Nrf2-Dependent Detoxification Pathway and Inhibits Benzo(a)pyrene Induced DNA Adducts in Lungs
Medicinal Chemistry Editorial [Hot Topic: Granulocyte Toxicity in the Lung (Guest Editor: Hannu Kankaanranta)]
Current Drug Targets - Inflammation & Allergy Transient Receptor Potential A1 Modulators
Current Topics in Medicinal Chemistry Biological Characteristics and Role of Histamine in Case of Allergic Rhinitis
Medicinal Chemistry Reviews - Online (Discontinued) Human Endotoxemia as a Model of Systemic Inflammation
Current Medicinal Chemistry Bacterial Conjunctivitis in Childhood: Etiology, Clinical Manifestations, Diagnosis, and Management
Recent Patents on Inflammation & Allergy Drug Discovery Clinical Implications of Recent Insights into the Structural Biology of Beta2 Adrenoceptors
Current Drug Targets Pidotimod and Immunological Activation in Individuals Infected with HIV
Current HIV Research Lung Structural Changes in Chronic Obstructive Pulmonary Diseases
Current Drug Targets - Inflammation & Allergy