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

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 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.

SUBMITTER: Monastyrskyi A

PROVIDER: S-EPMC5999544 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Monastyrskyi Andrii A Bayle Simon S Quereda Victor V Grant Wayne W Cameron Michael M Duckett Derek D Roush William W

Bioorganic & medicinal chemistry letters 20171213 3

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 here ...[more]

PMID: 29277458

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