Issue 10, 2014

Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitors

Abstract

The human kinome comprises over 500 protein kinases. When mutated or over-expressed, many play critical roles in abnormal cellular functions associated with cancer, cardiovascular disease and neurological disorders. Here we report a step-economical approach to designed kinase inhibitors inspired by the potent, but non-selective, natural product staurosporine, and synthetically enabled by a novel, complexity-increasing, serialized [5 + 2]/[4 + 2] cycloaddition strategy. This function-oriented synthesis approach rapidly affords tunable scaffolds, and produced a low nanomolar inhibitor of protein kinase C.

Graphical abstract: Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitors

Supplementary files

Article information

Article type
Research Article
Submitted
13 Leq 2014
Accepted
23 Way 2014
First published
06 Dit 2014
This article is Open Access
Creative Commons BY license

Org. Chem. Front., 2014,1, 1166-1171

Author version available

Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitors

P. A. Wender, A. D. Axtman, J. E. Golden, J. Kee, L. E. Sirois, R. V. Quiroz and M. C. Stevens, Org. Chem. Front., 2014, 1, 1166 DOI: 10.1039/C4QO00228H

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