MMP-13 selective alpha-sulfone hydroxamates: Identification of selective P1′ amides

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Fobian, Yvette M.^3,4  Freskos, John N.^3,4  Barta, Thomas E.^1,2  Bedell, Louis J.^1,2  Heintz, Robert^3,4  Kassab, Darren J.^3,4  Kiefer, James R.^3,4  Mischke, Brent V.^3,4  Molyneaux, John M.^3,4  Mullins, Patrick^3,4  Munie, Grace E.^3,4  Becker, Daniel P.^1,2 

[1] Pfizer Res & Dev, Dept Med Chem, Skokie, IL 60077 USA

[2] Pfizer Res & Dev, Dept Pharmacol, Skokie, IL 60077 USA

[3] Pfizer Res & Dev, Dept Med Chem, St Louis, MO 63198 USA

[4] Pfizer Res & Dev, Dept Pharmacol, St Louis, MO 63198 USA

关键词: MMP;    Matrix metalloproteinases;    MMP-13;    Arthritis inflammation;    Hydroxamic acids;   

DOI  :  10.1016/j.bmcl.2011.03.095

来源: Elsevier

【 摘 要 】

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. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

Free