Discovery of 2-arylquinazoline derivatives as a new class of ASK1 inhibitors. Issue 3 (1st February 2018)

• Record Type: Journal Article
• Authors: Monastyrskyi, Andrii; Bayle, Simon; Quereda, Victor; Grant, Wayne; Cameron, Michael; Duckett, Derek; Roush, William
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 3(2018)
• Page Start: 400
• Page End: 404
• Publication Date: 2018-02-01
• Subjects: Apoptosis signal-regulating kinase (ASK1) -- High throughput screening -- Structure-based drug design -- Kinase -- Inhibitor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.12.026
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 derivatives12 and23, with submicromolar inhibitory activities against ASK1. Kinetic analysis demonstrated that the 2-arylquinazoline scaffold ASK1 inhibitors described herein are ATP competitive.