- A selective matrix metalloprotease 12 inhibitor for potential treatment of chronic obstructive pulmonary disease (COPD): Discovery of (S)- 2-(8-(Methoxycarbonylamino)dibenzo[b,d]furan- 3-sulfonamido)-3-methylbutanoic acid (MMP408)
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Matrix metalloprotease 12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been found in the lung of human COPD patients. MMP408 (14), a potent and selective MMP-12 inhibitor, was derived from a potent matrix metalloprotease 2 and 13 inhibitor via lead optimization and has good physical properties and bioavailability. The compound blocks rhMMP-12-induced lung inflammation in a mouse model and was advanced for further development for the treatment of COPD.
- Wei, Li,Jianchang, Li,Yuchuan, Wu,Junjun, Wu,Hotchandani, Rajeev,Cunningham, Kristina,McFadyen, Iain,Bard, Joel,Morgan, Paul,Schlerman, Franklin,Xin, Xu,Tam, Steve,Goldman, Samuel J.,Williams, Cara,Sypek, Joseph,Mansour, Tarek S.
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supporting information; experimental part
p. 1799 - 1802
(2009/12/07)
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- Identification of an orally efficacious matrix metalloprotease 12 inhibitor for potential treatment of asthma
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MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing go
- Li, Wei,Li, Jianchang,Wu, Yuchuan,Rancati, Fabio,Vallese, Stefania,Raveglia, Luca,Wu, Junjun,Hotchandani, Rajeev,Fuller, Nathan,Cunningham, Kristina,Morgan, Paul,Fish, Susan,Krykbaev, Rustem,Xu, Xin,Tam, Steve,Goldman, Samuel J.,Abraham, William,Williams, Cara,Sypek, Joseph,Mansour, Tarek S.
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supporting information; experimental part
p. 5408 - 5419
(2010/02/28)
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- TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS
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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.
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Page/Page column 78
(2008/12/05)
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