Abstract
The CXC chemokine receptor 2 (CXCR2) has attracted a considerable amount of attention as a target for therapeutic intervention due the key role this receptor plays in a number of inflammatory disorders. Over the past decade, several classes of potent, selective CXCR2 receptor antagonists have been developed as potential anti-inflammatory agents. These small-molecule chemokine receptor antagonists have demonstrated the ability to inhibit CXCR2-mediated recruitment of inflammatory cells in vitro as well as shown efficacy in vivo in various animal models of inflammation. In addition, several of the most advanced CXCR2 receptor antagonists have recently demonstrated promising proof-of-activity results in early human clinical trials. This review details the discovery and development of the 3,4-diaminocyclobut-3- ene-1,2-dione-based CXCR2 receptor antagonist class including SCH 527123 which is currently in mid-stage clinical evaluation. The medicinal chemistry efforts leading to the discovery of SCH 527123, the in vitro and in vivo pharmacology for this compound, and an overview of the clinical evaluation of SCH 527123 will also be discussed.
Keywords: CXCR2, 3, 4-diaminocyclobut-3-ene-1, 2-dione, SCH 527123
Current Topics in Medicinal Chemistry
Title: Discovery of 3,4-Diaminocyclobut-3-ene-1,2-dione-Based CXCR2 Receptor Antagonists for the Treatment of Inflammatory Disorders
Volume: 10 Issue: 13
Author(s): Michael P. Dwyer and Purakattle Biju
Affiliation:
Keywords: CXCR2, 3, 4-diaminocyclobut-3-ene-1, 2-dione, SCH 527123
Abstract: The CXC chemokine receptor 2 (CXCR2) has attracted a considerable amount of attention as a target for therapeutic intervention due the key role this receptor plays in a number of inflammatory disorders. Over the past decade, several classes of potent, selective CXCR2 receptor antagonists have been developed as potential anti-inflammatory agents. These small-molecule chemokine receptor antagonists have demonstrated the ability to inhibit CXCR2-mediated recruitment of inflammatory cells in vitro as well as shown efficacy in vivo in various animal models of inflammation. In addition, several of the most advanced CXCR2 receptor antagonists have recently demonstrated promising proof-of-activity results in early human clinical trials. This review details the discovery and development of the 3,4-diaminocyclobut-3- ene-1,2-dione-based CXCR2 receptor antagonist class including SCH 527123 which is currently in mid-stage clinical evaluation. The medicinal chemistry efforts leading to the discovery of SCH 527123, the in vitro and in vivo pharmacology for this compound, and an overview of the clinical evaluation of SCH 527123 will also be discussed.
Export Options
About this article
Cite this article as:
P. Dwyer Michael and Biju Purakattle, Discovery of 3,4-Diaminocyclobut-3-ene-1,2-dione-Based CXCR2 Receptor Antagonists for the Treatment of Inflammatory Disorders, Current Topics in Medicinal Chemistry 2010; 10 (13) . https://dx.doi.org/10.2174/156802610791561246
DOI https://dx.doi.org/10.2174/156802610791561246 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
- Announcements
Related Articles
-
Molecular Targeting Agents in Renal Cell Carcinoma: Present Strategies and Future Perspectives
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Medicinal Chemistry Endoglin (CD105): A Target for Anti-angiogenetic Cancer Therapy
Current Drug Targets Organic Synthesis of C-Prenylated Phenolic Compounds
Current Organic Chemistry DNA Double Strand Break Repair - Related Synthetic Lethality
Current Medicinal Chemistry IgG4-Related Disease (IgG4+MOLPS) – Diagnostic Criteria and Diagnostic Problems
Current Immunology Reviews (Discontinued) Selenium Entities: Promising Scaffolds for the Treatment of Cancer and Leishmania
Current Organic Synthesis The Inverse Relationship Between Cancer and Alzheimer's Disease: A Possible Mechanism
Current Alzheimer Research Reprogrammed Metabolism of Cancer Cells as a Potential Therapeutic Target
Current Pharmaceutical Design Thymoquinone Shows the Diverse Therapeutic Actions by Modulating Multiple Cell Signaling Pathways: Single Drug for Multiple Targets
Current Pharmaceutical Biotechnology The Impact of Tumor Physiology on Camptothecin-Based Drug Development
Current Medicinal Chemistry - Anti-Cancer Agents Recent Applications of Benzimidazole as a Privileged Scaffold in Drug Discovery
Mini-Reviews in Medicinal Chemistry Plasminogen Activator Inhibitor-1 in Tumor Growth, Angiogenesis and Vascular Remodeling
Current Pharmaceutical Design Risk Factors for Lung Cancer in Never Smokers: A Recent Review Including Genetics
Current Respiratory Medicine Reviews The Functions of Histone Modification Enzymes in Cancer
Current Protein & Peptide Science T Cell Receptor Bias in Humans
Current Immunology Reviews (Discontinued) Prolyl Peptidases Related to Dipeptidyl Peptidase IV: Potential of Specific Inhibitors in Drug Discovery.
Current Topics in Medicinal Chemistry Cell Death: Tipping the Balance of Autoimmunity and Tissue Repair
Current Pharmaceutical Design Adenosine Receptors as Novel Targets for the Treatment of Various Cancers
Current Pharmaceutical Design Chemical Connexin Impairment in the Developing Gonad Associated with Offspring Infertility
Current Medicinal Chemistry