MMP-13 selective alpha-sulfone hydroxamates: identification of selective P1' amides

Yvette M Fobian; John N Freskos; Thomas E Barta; Louis J Bedell; Robert Heintz; Darren J Kassab; James R Kiefer; Brent V Mischke; John M Molyneaux; Patrick Mullins; Grace E Munie; Daniel P Becker

doi:10.1016/j.bmcl.2011.03.095

MMP-13 selective alpha-sulfone hydroxamates: identification of selective P1' amides

Bioorg Med Chem Lett. 2011 May 15;21(10):2823-5. doi: 10.1016/j.bmcl.2011.03.095. Epub 2011 Apr 1.

Authors

Yvette M Fobian¹, John N Freskos, Thomas E Barta, Louis J Bedell, Robert Heintz, Darren J Kassab, James R Kiefer, Brent V Mischke, John M Molyneaux, Patrick Mullins, Grace E Munie, Daniel P Becker

Affiliation

¹ Department of Medicinal Chemistry, Pfizer Research & Development, 700 Chesterfield Village Parkway, St. Louis, MO 63198, USA.

PMID: 21493063
DOI: 10.1016/j.bmcl.2011.03.095

Abstract

Continuing our interest in designing compounds preferentially potent and selective for MMP-13, we report on a series of hydroxamic acids with a flexible amide P1' substituents. We identify an amide which spares both MMP-1 and -14, and shows >500 fold selectivity for MMP-13 versus MMP-2 and -8.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Humans
Hydroxamic Acids / chemical synthesis*
Hydroxamic Acids / chemistry
Inhibitory Concentration 50
Matrix Metalloproteinase Inhibitors*
Molecular Structure
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Structure-Activity Relationship
Substrate Specificity

Substances

Amides
Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Protease Inhibitors