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)

  • J Med Chem. 2009 Apr 9;52(7):1799-802. doi: 10.1021/jm900093d.
Wei Li  1 ,  Jianchang Li ,  Yuchuan Wu ,  Junjun Wu ,  Rajeev Hotchandani ,  Kristina Cunningham ,  Iain McFadyen ,  Joel Bard ,  Paul Morgan ,  Franklin Schlerman ,  Xin Xu ,  Steve Tam ,  Samuel J Goldman ,  Cara Williams ,  Joseph Sypek ,  Tarek S Mansour
Affiliations
  • 1. Chemical Sciences, Inflammation, and Drug Safety and Metabolism, Wyeth Research, Cambridge, Massachusetts 02140, USA.
PMID: 19278250 DOI: 10.1021/jm900093d
Abstract

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.

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