Title of article
Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors
Author/Authors
Michael A. Letavic، نويسنده , , Matt Z. Axt، نويسنده , , John T. Barberia، نويسنده , , Thomas J. Carty، نويسنده , , Dennis E. Danley، نويسنده , , Kieran F. Geoghegan، نويسنده , , Nadia S. Halim، نويسنده , , Lise R. Hoth، نويسنده , , Ajith V. Kamath، نويسنده , , Ellen R. Laird، نويسنده , , Lori L. Lopresti-Morrow، نويسنده , , Kim F. McClure، نويسنده , , Peter G. Mitchell، نويسنده , , Vijayalakshmi Natarajan، نويسنده , , Mark C. Noe، نويسنده , , Jayvardhan Pandit، نويسنده , , Lisa Reeves، نويسنده , , Gayle K. Schulte، نويسنده , , Sheri L. Snow، نويسنده , , Francis J. Sweeney، نويسنده , , et al.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2002
Pages
4
From page
1387
To page
1390
Abstract
A series of novel, selective TNF-α converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1′ site of the enzyme. Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with >100× selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-α release in LPS-treated human whole blood.
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2002
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
792222
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