| Literature DB >> 11992783 |
Michael A Letavic1, Matt Z Axt, John T Barberia, Thomas J Carty, Dennis E Danley, Kieran F Geoghegan, Nadia S Halim, Lise R Hoth, Ajith V Kamath, Ellen R Laird, Lori L Lopresti-Morrow, Kim F McClure, Peter G Mitchell, Vijayalakshmi Natarajan, Mark C Noe, Jayvardhan Pandit, Lisa Reeves, Gayle K Schulte, Sheri L Snow, Francis J Sweeney, Douglas H Tan, Chul H Yu.
Abstract
A series of novel, selective TNF-alpha 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 >100x 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-alpha release in LPS-treated human whole blood.Entities:
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Year: 2002 PMID： 11992783 DOI： 10.1016/s0960-894x(02)00183-x
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823