当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD).

Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD).

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wu Y,Li J,Wu J,Morgan P,Xu X,Rancati F,Vallese S,Raveglia L,Hotchandani R,Fuller N,Bard J,Cunningham K,Fish S,Krykbaev R,Tam S,Goldman SJ,Williams C,Mansour TS,Saiah E,Sypek J,Li W

doi

10.1016/j.bmcl.2011.11.046

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

138-43

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01590-3

journal_volume

22

pub_type

杂志文章

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