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Bioorg Med Chem Lett. 2010 Jan 15;20(2):576-80. doi: 10.1016/j.bmcl.2009.11.081. Epub 2009 Nov 22.

Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.

Author information

1
Global Research and Development, Pfizer Inc., 700 Chesterfield Parkway West, St. Louis, MO 63017, USA. mark.e.schnute@pfizer.com

Abstract

Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)(') active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model.

PMID:
20005097
DOI:
10.1016/j.bmcl.2009.11.081
[Indexed for MEDLINE]

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