Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. The disease ranks among the top five leading causes of death worldwide. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. A wide variety of potent and selective MMP-12 compounds, which have a tricyclic scaffold with sulfonamide attached to an amino acid, had been synthesized.

Synthesis and SAR of potent & selective MMP-12 inhibitors

241st National Meeting (2011)

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