Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix metalloproteinase inhibitors.

Abstract:

:Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that have been implicated in various disease processes. Different classes of MMP inhibitors, including hydroxamic acids, phosphinic acids and thiols, have been previously described. Most of these mimic peptides and most likely bind in a similar way to the corresponding peptide substrates. Here we describe pyrimidine-triones as a completely new class of metalloprotease inhibitors. While the pyrimidine-trione template is used as the zinc-chelating moiety, the substituents have been optimized to yield inhibitors comparable in their inhibition efficiency of matrix metalloproteinases to hydroxamic acid derivatives such as batimastat. However, they are much more specific for a small subgroup of MMPs, namely the gelatinases (MMP-2 and MMP-9).

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Grams F,Brandstetter H,D'Alò S,Geppert D,Krell HW,Leinert H,Livi V,Menta E,Oliva A,Zimmermann G,Gram F,Brandstetter H,D'Alò S,Geppert D,Krell HW,Leinert H,Livi VMenta E,Oliva A,Zimmermann G

doi

10.1515/BC.2001.159

keywords:

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

1277-85

issue

8

eissn

1431-6730

issn

1437-4315

journal_volume

382

pub_type

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