Potent and selective carboxylic acid-based inhibitors of matrix metalloproteinases

Authors
Pikul, S Ohler, NE Ciszewski, G Laufersweiler, MC Almstead, NG De, B Natchus, MG Hsieh, LC Janusz, MJ Peng, SX Branch, TM King, SL Taiwo, YO Mieling, GE
Citation
S. Pikul et al., Potent and selective carboxylic acid-based inhibitors of matrix metalloproteinases, J MED CHEM, 44(16), 2001, pp. 2499-2502
Citations number
26
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
00222623 → ACNP
Volume
44
Issue
16
Year of publication
2001
Pages
2499 - 2502
Database
ISI
SICI code
0022-2623(20010802)44:16<2499:PASCAI>2.0.ZU;2-V
Abstract
A novel series of carboxylic acids containing a substituted piperidine were synthesized and tested for inhibition of selected matrix metalloproteinase s. Multiple analogues prepared based on this novel design were found to inh ibit the target MMPs (MMP-2, -3, -8, -9, and -13) with unprecedented, low n anomolar potency while, at the same time, sparing MMP-1 and MMP-7. Solubili ty and plasma protein binding of several members of this new series of carb oxylic acids were also investigated.