A three-step synthesis from rebeccamycin of an efficient checkpoint kinase 1 inhibitor.
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.
Anizon
Fabrice
F
Université Blaise Pascal, Synthèse et Etude de Systèmes à Intérêt Biologique, UMR 6504 du CNRS, 63177 Aubière, France.
Golsteyn
Roy M
RM
Léonce
Stéphane
S
Pfeiffer
Bruno
B
Prudhomme
Michelle
M
D000818:Animals; D002227:Carbazoles / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry; D000071877:Checkpoint Kinase 1; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis*; D011494:Protein Kinases / Q000187:drug effects*
D002227:Carbazoles; D002241:Carbohydrates; D007211:Indoles; D047428:Protein Kinase Inhibitors; C053339:rebeccamycin; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1