Pyrrolocarbazoles as checkpoint 1 kinase inhibitors.
The carbazole framework is found in many natural compounds of biological interest. Indolocarbazoles such as rebeccamycin and staurosporine which are either a topoisomerase I inhibitor (rebeccamycin) or a non selective kinase inhibitor (staurosporine) are bacterial metabolites. In the search for new antitumor agents, DNA damage checkpoint kinases, in particular Checkpoint kinase 1, have recently emerged as attractive targets for cancer therapy. This review reports the synthesis and Chk1 inhibitory activities of pyrrolocarbazole compounds bearing four or five fused rings.
Hénon
Hélène
H
Laboratoire SEESIB, Université Blaise Pascal, UMR 6504 du CNRS, 24 Avenue des Landais, 63177 Aubière, France. Michelle.PRUDHOMME@univ-bpclermont.fr
Conchon
Elisabeth
E
Hugon
Bernadette
B
Messaoudi
Samir
S
Golsteyn
Roy M
RM
Prudhomme
Michelle
M
D002227:Carbazoles / Q000494:pharmacology*; D000071877:Checkpoint Kinase 1; D003500:Cyclization; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry; D008954:Models, Biological; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D002227:Carbazoles; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C029899:imidazole; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1