Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitorsDedicated to Max Malacria, a friend and scholar whose science and creative contributions to step-economical synthesis have inspired us all and moved the field closer to the ideal.Electronic supplementary information (ESI) available: Synthetic procedures and spectral data. See DOI: 10.1039/c4qo00228hClick here for additional data file.
Org Chem Front
; 1(10): 1166-1171, 2014 Dec 29.
Article
em En
| MEDLINE
| ID: mdl-25632347
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Health_economic_evaluation
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article