Andersen Jacob Lauwring, Lindberg Samsa, Langgård Morten, Maltas Philip J, Rønn Lars Christian Biilmann, Bundgaard Christoffer, Strandbygaard Dorthe, Thirup Søren, Watson Stephen P
The Lundbeck Foundation Research Centre MIND, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, Aarhus C 8000, Denmark; Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus C 8000, Denmark.
Neuroscience Drug Discovery, H- Lundbeck A/S, Copenhagen, Denmark.
Bioorg Med Chem Lett. 2017 Jun 1;27(11):2629-2633. doi: 10.1016/j.bmcl.2017.02.028. Epub 2017 Feb 20.
Using fragment based and structure based drug discovery strategies a series of novel Sortilin inhibitors has been identified. The inhibitors are based on the N-substituted 1,2,3-triazol-4-one/ol heterocyclic template. X-ray crystallography shows that the 1,2,3-triazol-4-one/ol acts as a carboxylic acid isostere, making a bi-dentate interaction with an arginine residue of Sortilin, an interaction which has not been previously characterised for this heterocycle.
通过基于片段和基于结构的药物发现策略，已鉴定出一系列新型Sortilin抑制剂。这些抑制剂基于N-取代的1,2,3-三唑-4-酮/醇杂环模板。X射线晶体学表明，1,2,3-三唑-4-酮/醇作为羧酸生物电子等排体，与Sortilin的精氨酸残基形成双齿相互作用，这种相互作用此前尚未针对该杂环进行过表征。
