Pyrimidine-2,4,6-triones:: A new effective and selective class of matrix metalloproteinase inhibitors
Pyrimidine-2,4,6-triones:: A new effective and selective class of matrix metalloproteinase inhibitors
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DOI：
10.1515/bc.2001.159
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发表时间：
2001-08-01
影响因子：
3.7
通讯作者：
Zimmermann, G
中科院分区：
文献类型：
--
作者：
Grams, F;Brandstetter, H;Zimmermann, G
基质金属蛋白酶(MMPs)是一类锌内肽酶家族，参与多种疾病过程。不同类别的基质金属蛋白酶抑制剂，包括异羟肟酸、膦酸和硫醇，以前已经被描述过。大多数这些模拟多肽很可能以类似的方式与相应的多肽底物结合。在此，我们将嘧啶三酮类化合物描述为一类全新的金属蛋白酶抑制剂。当使用嘧啶-三酮模板作为锌螯合部分时，取代基已被优化以产生与异羟肟酸衍生物(如巴替马斯特)相当的基质金属蛋白酶抑制效率的抑制剂。然而，它们对一小部分MMPs更具特异性，即明胶酶(MMP2和MMP9)。
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 desccribe 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).