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.
MeSH terms
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Adenosine Triphosphate / chemistry
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Binding Sites
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Carbazoles / chemical synthesis*
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Carbazoles / chemistry
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Carbazoles / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Checkpoint Kinase 1
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Humans
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Imides / chemistry
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinases / metabolism*
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Pyrroles / chemistry*
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Structure-Activity Relationship
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / metabolism
Substances
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Carbazoles
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Imides
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Protein Kinase Inhibitors
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Pyrroles
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Adenosine Triphosphate
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Protein Kinases
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src-Family Kinases
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CHEK1 protein, human
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Checkpoint Kinase 1