A three-step synthesis from rebeccamycin of an efficient checkpoint kinase 1 inhibitor

Fabrice Anizon; Roy M Golsteyn; Stéphane Léonce; Bruno Pfeiffer; Michelle Prudhomme

doi:10.1016/j.ejmech.2008.05.023

A three-step synthesis from rebeccamycin of an efficient checkpoint kinase 1 inhibitor

Eur J Med Chem. 2009 May;44(5):2234-8. doi: 10.1016/j.ejmech.2008.05.023. Epub 2008 Jul 3.

Authors

Fabrice Anizon¹, Roy M Golsteyn, Stéphane Léonce, Bruno Pfeiffer, Michelle Prudhomme

Affiliation

¹ Université Blaise Pascal, Synthèse et Etude de Systèmes à Intérêt Biologique, UMR 6504 du CNRS, 63177 Aubière, France.

PMID: 18602198
DOI: 10.1016/j.ejmech.2008.05.023

Abstract

Rebeccamycin derivative 1 bearing a sugar moiety linked to both indole nitrogens and an amino substituent on the carbohydrate unit was synthesized in three steps from the bacterial metabolite. This compound was found to be a highly potent checkpoint kinase 1 inhibitor with an IC(50) value of 2.8nM.

MeSH terms

Animals
Carbazoles / chemistry*
Carbohydrates / chemistry
Checkpoint Kinase 1
Humans
Indoles / chemistry
Inhibitory Concentration 50
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinases / drug effects*

Substances

Carbazoles
Carbohydrates
Indoles
Protein Kinase Inhibitors
rebeccamycin
Protein Kinases
CHEK1 protein, human
Checkpoint Kinase 1