Discovery of 2-arylquinazoline derivatives as a new class of ASK1 inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Monastyrskyi, Andrii¹  Bayle, Simon²  Quereda, Victor²  Grant, Wayne²  Cameron, Michael²  Duckett, Derek²  Roush, William¹ 

[1] Scripps Florida, Dept Chem, 130 Scripps Way, Jupiter, FL 33458 USA

[2] Scripps Florida, Dept Mol Med, 130 Scripps Way, Jupiter, FL 33458 USA

关键词: Apoptosis signal-regulating kinase (ASK1);    High throughput screening;    Structure-based drug design;    Kinase;    Inhibitor;   

DOI  :  10.1016/j.bmcl.2017.12.026

来源: Elsevier

【 摘 要 】

The development of a new series of apoptosis signal-regulating kinase 1 (ASK1) inhibitors is described. Starting from purine, pyrimidine and quinazoline scaffolds identified by high throughput screening, we used tools of structure-based drug design to develop a series of potent kinase inhibitors, including 2-arylquinazoline derivatives 12 and 23, with submicromolar inhibitory activities against ASK1. Kinetic analysis demonstrated that the 2-arylquinazoline scaffold ASK1 inhibitors described herein are ATP competitive. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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