Abstract
Three different classes of aryl hydroxamic acid scaffolds have been explored and provided potent inhibitors of MMP-1, -2, -9, -13 and TACE. Structure-based design has allowed the evolution of these inhibitors from broad spectrum inhibitors into compounds that are more selective for MMPs relevant to particular disease states. Aryl hydroxamates selective for MMP-9, MMP-13 and TACE have been disclosed that may aid in the study of the physiological role of these enzymes. Furthermore, the different selectivity profiles offered by these MMP / TACE inhibitors may allow the determination of which metalloprotease, or group of metalloproteases, must be inhibited for the safe, long-term treatment of osteoarthritis, rheumatoid arthritis and cancer. Some of these compounds have demonstrated useful biological activity in efficacy models relevant to osteoarthritis and rheumatoid arthritis and are therefore potential clinical candidates.
Keywords: aryl hydroxamic acids, aryl hydroxamates, mmp inhibitor, tace inhibitor, anthranilic acid
Current Topics in Medicinal Chemistry
Title: The Design and Synthesis of Aryl Hydroxamic Acid Inhibitors of MMPs and TACE
Volume: 4 Issue: 12
Author(s): Jeremy I. Levin
Affiliation:
Keywords: aryl hydroxamic acids, aryl hydroxamates, mmp inhibitor, tace inhibitor, anthranilic acid
Abstract: Three different classes of aryl hydroxamic acid scaffolds have been explored and provided potent inhibitors of MMP-1, -2, -9, -13 and TACE. Structure-based design has allowed the evolution of these inhibitors from broad spectrum inhibitors into compounds that are more selective for MMPs relevant to particular disease states. Aryl hydroxamates selective for MMP-9, MMP-13 and TACE have been disclosed that may aid in the study of the physiological role of these enzymes. Furthermore, the different selectivity profiles offered by these MMP / TACE inhibitors may allow the determination of which metalloprotease, or group of metalloproteases, must be inhibited for the safe, long-term treatment of osteoarthritis, rheumatoid arthritis and cancer. Some of these compounds have demonstrated useful biological activity in efficacy models relevant to osteoarthritis and rheumatoid arthritis and are therefore potential clinical candidates.
Export Options
About this article
Cite this article as:
Levin I. Jeremy, The Design and Synthesis of Aryl Hydroxamic Acid Inhibitors of MMPs and TACE, Current Topics in Medicinal Chemistry 2004; 4 (12) . https://dx.doi.org/10.2174/1568026043387935
DOI https://dx.doi.org/10.2174/1568026043387935 |
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
-
Carbohydrate-Metal Complexes and their Potential as Anticancer Agents
Current Medicinal Chemistry The Effect of Neuropathic Pain Symptoms on Remission in Patients with Early Rheumatoid Arthritis
Current Rheumatology Reviews Role of Innate Immunity in Triggering and Tuning of Autoimmune Diabetes
Current Molecular Medicine Successful Treatment for Severe Thyroid-associated Ophthalmopathy with Tocilizumab
Endocrine, Metabolic & Immune Disorders - Drug Targets Property-Based Design of KDR Kinase Inhibitors
Current Medicinal Chemistry Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)
Current Medicinal Chemistry Current Studies of Osteoclastogenesis and Potential Drug Targets
Current Drug Targets From the Table to the Bedside: Can Food-Derived Sulforaphane be used as a Novel Agent to Treat Leukemia?
Current Cancer Drug Targets Epigenetic and Disease Targets by Polyphenols
Current Pharmaceutical Design CD93: Recent Advances and Implications in Disease
Current Drug Targets Editorial (Asia-Pacific Health 2020 and Genomics without Borders: Co-Production of Knowledge by Science and Society Partnership for Global Personalized Medicine)
Current Pharmacogenomics and Personalized Medicine Determination of Phytochemicals by GC-MS in Two Fractions (17 and 21) of Methanol Extract of Loranthus Micranthus and their Antioxidant and Anti-Inflammatory Activity
The Natural Products Journal Suppression of NF-κB Activation By Gentian Violet Promotes Osteoblastogenesis and Suppresses Osteoclastogenesis
Current Molecular Medicine Novel Approaches to Study the Involvement of α7-nAChR in Human Diseases
Current Drug Targets Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases
Current Drug Targets Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design Pulmonary Hypertension and Lung Transplant in Connective Tissue Disease-Interstitial Lung Disease
Current Respiratory Medicine Reviews Immune Thrombocytopenic Purpura: New Biological Therapy of an Old Disease
Current Medicinal Chemistry An update on Anti-inflammatory Compounds: A Review
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Effects of ACE Inhibitors on Skeletal Muscle
Current Pharmaceutical Design