Abstract
Background: The benzoxazepine JL13 is an analogue of the clozapine family of antipsychotic agents which target the 5-HT2A receptor, and has showed promise as an atypical antipsychotic agent. Based on the dearth of clinically effective anti-psychotic agents available, we sought to design and chemically synthesize additional analogues.
Methods: Structure function analysis was conducted using state of art computational methods, which were designed to highlight new candidates for chemical synthesis. Efficient syntheses were then conducted and the products screened for affinity to the receptor.
Results: Among many new analogues prepared, an aza analogue demonstrated seventeen times greater affinity for the receptor than JL13.
Conclusion: An efficient synthetic route to an aza-analogue of JL13 was developed and will allow rapid modifications of the core and synthesis of related libraries.
Keywords: 5HT receptor, antipsychotic, clozapine, diazepine, JL13, synthesis.
Central Nervous System Agents in Medicinal Chemistry
Title:Homology Modeling Inspired Synthesis of 5-HT2A Receptor Inhibitors: A Diazepine Analogue of the Atypical Antipsychotic JL13
Volume: 17 Issue: 3
Author(s): Enrico Mongeau, Gengyang Yuan, Zachary Minden, Scott Waldron, Raymond Booth, Daniel Felsing, Mary J. Ondrechen and Graham B. Jones*
Affiliation:
- Clinical and Translational Science Institute, Tufts University Medical Center, 800 Washington Street, Boston, MA 02111,United States
Keywords: 5HT receptor, antipsychotic, clozapine, diazepine, JL13, synthesis.
Abstract: Background: The benzoxazepine JL13 is an analogue of the clozapine family of antipsychotic agents which target the 5-HT2A receptor, and has showed promise as an atypical antipsychotic agent. Based on the dearth of clinically effective anti-psychotic agents available, we sought to design and chemically synthesize additional analogues.
Methods: Structure function analysis was conducted using state of art computational methods, which were designed to highlight new candidates for chemical synthesis. Efficient syntheses were then conducted and the products screened for affinity to the receptor.
Results: Among many new analogues prepared, an aza analogue demonstrated seventeen times greater affinity for the receptor than JL13.
Conclusion: An efficient synthetic route to an aza-analogue of JL13 was developed and will allow rapid modifications of the core and synthesis of related libraries.
Export Options
About this article
Cite this article as:
Mongeau Enrico , Yuan Gengyang , Minden Zachary , Waldron Scott, Booth Raymond , Felsing Daniel, Ondrechen J. Mary and Jones B. Graham*, Homology Modeling Inspired Synthesis of 5-HT2A Receptor Inhibitors: A Diazepine Analogue of the Atypical Antipsychotic JL13, Central Nervous System Agents in Medicinal Chemistry 2017; 17 (3) . https://dx.doi.org/10.2174/1871524917666170426123607
DOI https://dx.doi.org/10.2174/1871524917666170426123607 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
- 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
-
Experimental Rodent Models of Vascular Dementia: A Systematic Review
CNS & Neurological Disorders - Drug Targets Characterization of Cancer Stem Cells and Primary Cilia in Medulloblastoma
CNS & Neurological Disorders - Drug Targets Vasoactive Factors and Diabetic Retinopathy: Vascular Endothelial Growth Factor, Cycoloxygenase-2 and Nitric Oxide
Current Pharmaceutical Design Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases
Current Alzheimer Research Ferulic Acid-Loaded Lipid Nanostructures as Drug Delivery Systems for Alzheimers Disease: Preparation, Characterization and Cytotoxicity Studies
Current Nanoscience Challenging the Current Approaches to Multiple Myeloma-Related Bone Disease: From Bisphosphonates to Target Therapy
Current Cancer Drug Targets Creating Change: How Knowledge Translates into Action for Protecting Babies from Sudden Infant Death?
Current Pediatric Reviews Clinical Features of Scleroderma-Like Disorders: A Challenge for the Rheumatologist
Current Rheumatology Reviews Neuroimaging of Non-Accidental Injury
Current Pediatric Reviews Meet Our Editorial Board Member
Current Neuropharmacology Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry Advances in Titanium-Catalyzed Synthesis of Chiral Sulfoxide Drugs
Mini-Reviews in Organic Chemistry Catatonia: A Narrative Review
Central Nervous System Agents in Medicinal Chemistry Gastrointestinal Hemorrhage is Associated with Mortality after Acute Ischemic Stroke
Current Neurovascular Research Time Recall; Future Concept of Chronomodulating Chemotherapy for Cancer
Current Pharmaceutical Biotechnology Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development
Current Topics in Medicinal Chemistry Current Status of Rho-Associated Kinases (ROCKs) in Coronary Atherosclerosis and Vasospasm
Cardiovascular & Hematological Agents in Medicinal Chemistry Cannabinoid Receptors as Therapeutic Targets
Current Pharmaceutical Design Anti-Inflammatory Effects of C-Peptide Prevent Endothelial Dysfunction in Type 1 Diabetes
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cannabis Use and Psychosis: Theme Introduction
Current Pharmaceutical Design