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Identification of novel, exosite-binding matrix metalloproteinase-13 inhibitor scaffolds.

Abstract：

:Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhibitor 4, discovered through high-throughput screening, were synthesized to investigate structure-activity relationships in this inhibitor series. Systematic modifications of 4 led to the discovery of MMP-13 inhibitors 20 and 24 which are more selective than 4 against other MMPs. Compound 20 is also approximately fivefold more potent as an MMP-13 inhibitor than the original HTS-derived lead compound 4.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Roth J,Minond D,Darout E,Liu Q,Lauer J,Hodder P,Fields GB,Roush WR

doi

10.1016/j.bmcl.2011.09.077

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

7180-4

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01321-7

journal_volume

21

pub_type

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