title: Synthesis, checkpoint kinase 1 inhibitory properties and in vitro antiproliferative activities of new pyrrolocarbazoles.
abstract: In the course of structure-activity relationship studies on granulatimide analogues, new pyrrolo[3,4-c]carbazoles have been synthesized in which the imidazole heterocycle was replaced by a five-membered ring lactam system or a dimethylcyclopentanedione. Moreover, the synthesis of an original structure in which a sugar moiety is attached to the indole nitrogen and to a six-membered D ring via an oxygen is reported. The inhibitory activities of the newly synthesized compounds toward checkpoint kinase 1 and their in vitro antiproliferative activities toward three tumor cell lines: murine leukemia L1210, and human colon carcinoma HT29 and HCT116 are described.
authors.affiliation: Laboratoire SEESIB, Université Blaise Pascal, UMR 6504 du CNRS, 63177 Aubière, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Conchon
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.forename: Bettina
authors.initials: B
authors.lastname: Aboab
authors.forename: Roy M
authors.initials: RM
authors.lastname: Golsteyn
authors.forename: Stéphane
authors.initials: S
authors.lastname: Léonce
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Michelle
authors.initials: M
authors.lastname: Prudhomme
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D006801:Humans; D007094:Imides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002227:Carbazoles; D007094:Imides; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D019061:src-Family Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1