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.
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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 |
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