Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective alpha-sulfone hydroxamates

Stephen A Kolodziej; Susan L Hockerman; Terri L Boehm; Jeffery N Carroll; Gary A DeCrescenzo; Joseph J McDonald; Debbie A Mischke; Grace E Munie; Theresa R Fletcher; Joseph G Rico; Nathan W Stehle; Craig Swearingen; Daniel P Becker

doi:10.1016/j.bmcl.2010.04.130

Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective alpha-sulfone hydroxamates

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3557-60. doi: 10.1016/j.bmcl.2010.04.130. Epub 2010 May 23.

Authors

Stephen A Kolodziej¹, Susan L Hockerman, Terri L Boehm, Jeffery N Carroll, Gary A DeCrescenzo, Joseph J McDonald, Debbie A Mischke, Grace E Munie, Theresa R Fletcher, Joseph G Rico, Nathan W Stehle, Craig Swearingen, Daniel P Becker

Affiliation

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

PMID: 20529684
DOI: 10.1016/j.bmcl.2010.04.130

Abstract

A series of phenyl piperidine alpha-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats.

MeSH terms

Administration, Oral
Animals
Biological Availability
Hydroxamic Acids / administration & dosage
Matrix Metalloproteinase 1 / drug effects
Matrix Metalloproteinase 14 / drug effects
Matrix Metalloproteinase Inhibitors*
Piperidines
Rats
Small Molecule Libraries
Solubility
Substrate Specificity
Sulfones

Substances

Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Piperidines
Small Molecule Libraries
Sulfones
Matrix Metalloproteinase 1
Matrix Metalloproteinase 14