Tertiary‐Amine‐Based Inhibitors of the Astacin Protease Meprin α,ChemMedChem

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Tertiary‐Amine‐Based Inhibitors of the Astacin Protease Meprin α
ChemMedChem ( IF 3.6 ) Pub Date : 2018-07-16 , DOI: 10.1002/cmdc.201800300
Kathrin Tan ₁ , Christian Jäger ₁ , Dagmar Schlenzig ₁ , Stephan Schilling ₁ , Mirko Buchholz ₁ , Daniel Ramsbeck ₁

Affiliation

Metalloproteinases of the astacin family are drawing ever increasing attention as potential drug targets. However, knowledge regarding inhibitors thereof is limited in most cases. Crucial for the development of metalloprotease inhibitors is high selectivity, to avoid side effects brought about by inhibition of off‐target proteases and interference with physiological pathways. In this study we aimed at the design of novel selective inhibitors for the astacin proteinase meprin α. Based on a recently identified tertiary amine scaffold, a series of compounds was synthesized and evaluated. The compounds exhibit reasonable inhibitory activity with high selectivity over other metalloproteases. The isoenzyme meprin β is only slightly inhibited. Hence, the present study revealed a novel class of selective meprin α inhibitors with improved selectivity over known compounds.

中文翻译：

基于叔胺的Astacin蛋白酶Meprinα抑制剂

作为潜在的药物靶标，Astacin家族的金属蛋白酶越来越受到关注。但是，在大多数情况下，关于其抑制剂的知识是有限的。开发金属蛋白酶抑制剂的关键是高选择性，以避免因脱靶蛋白酶的抑制和对生理途径的干扰而带来的副作用。在这项研究中，我们的目标是设计一种新的选择性抑制剂，以用于阿斯巴星蛋白酶meprinα。基于最近鉴定的叔胺支架，合成并评估了一系列化合物。与其他金属蛋白酶相比，该化合物具有合理的抑制活性和高选择性。同工酶甲羟乙炔β仅受到轻微抑制。因此，

更新日期：2018-07-16

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