1025717-75-2Relevant articles and documents
Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD)
Wu, Yuchuan,Li, Jianchang,Wu, Junjun,Morgan, Paul,Xu, Xin,Rancati, Fabio,Vallese, Stefania,Raveglia, Luca,Hotchandani, Rajeev,Fuller, Nathan,Bard, Joel,Cunningham, Kristina,Fish, Susan,Krykbaev, Rustem,Tam, Steve,Goldman, Samuel J.,Williams, Cara,Mansour, Tarek S.,Saiah, Eddine,Sypek, Joseph,Li, Wei
scheme or table, p. 138 - 143 (2012/02/16)
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. 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. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status.
TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS
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Page/Page column 103; 121, (2008/12/05)
The present invention relates to compositions of the formula (I): and pharmaceutically acceptable salts, hydrates, or esters thereof, wherein R1, R2, R3, R4, R5, X, and Y are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating pathologic conditions or disorders mediated wholly or in part by matrix metalloproteinases, such as asthma and chronic obstructive pulmonary disease, comprising administering a therapeutically effective amount of a compound of formula (I) to a mammal (e.g., a human) in need thereof.