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通过构建涉及苯并噻唑核心的分子内氢键来设计和合成构象受限的Dyrk1A抑制剂。

Design and synthesis of conformationally constraint Dyrk1A inhibitors by creating an intramolecular H-bond involving a benzothiazole core.

作者信息

Salah Mohamed, Abdel-Halim Mohammad, Engel Matthias

机构信息

Pharmaceutical and Medicinal Chemistry , Saarland University , Campus C2.3 , D-66123 Saarbrücken , Germany . Email:

Department of Pharmaceutical Chemistry , Faculty of Pharmacy and Biotechnology , German University in Cairo , Cairo 11835 , Egypt.

出版信息

Medchemcomm. 2018 May 28;9(6):1045-1053. doi: 10.1039/c8md00142a. eCollection 2018 Jun 1.

DOI:10.1039/c8md00142a
PMID:30108993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6071757/
Abstract

We present the development of conformationally pre-organised Dyrk1A inhibitors based on the hydroxybenzothiazole urea scaffold. The modifications introduced to the discovered hit (AHS-211) proved the crucial role of the urea linker to preserve the bioactive conformation and led to the development of compound as a promising selective Dyrk1A inhibitor.

摘要

我们展示了基于羟基苯并噻唑脲支架的构象预组织的Dyrk1A抑制剂的开发。对发现的活性化合物（AHS-211）进行的修饰证明了脲连接基在保持生物活性构象方面的关键作用，并导致了化合物作为一种有前景的选择性Dyrk1A抑制剂的开发。

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