MEDI 26 |
| Matrix metalloproteinases (MMPs) belong to a family of zinc-containing enzymes that regulate the turnover of extra-cellular matrix proteins and activity of a number of pro-inflammatory mediators. Abnormal enzymatic activity of macrophage metalloelastase (MMP-12), one member of the MMP superfamily, is implicated in the development of cigarette smoke-induced emphysema, a hallmark of chronic obstructive pulmonary disease (COPD). Inhibition of MMP-12 therefore represents an attractive therapeutic strategy in the treatment of COPD. The clinical utility of broad-spectrum MMP inhibitors has been limited by musculoskeletal side effects and lack of selectivity is one possible explanation to this adverse effect, although the mechanism remains unclear. Most known MMP inhibitors possess a hydroxamic acid moiety, a strong Zn (II)-binding group, which leads to their high-affinity binding to the enzymatic sites of MMPs. Hydroxy hydantoins, a novel class of MMP inhibitors, interacts with the enzymes via a weak Zn (II)-binding group and the development of potent MMP-12 inhibitors from this series will be presented. |
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General Oral Session
1:30 PM-4:50 PM, Sunday, August 19, 2007 BCEC -- 210A, Oral
Division of Medicinal Chemistry |