Abstract
This communication reports a new synthetic route of pyridopyrimidines to facilitate their structural optimization in a library fashion and describes the development of pyridopyrimidines that have excellent enzymatic and cell potency against Akt1 and Akt2. This series also shows a high level of selectivity over other closely related kinases and significantly improved caspase-3 activity with the more optimized compounds.
MeSH terms
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Amines / chemical synthesis
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Amines / chemistry
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Amines / pharmacology
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Caspase 3 / metabolism
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Humans
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Inhibitory Concentration 50
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Piperidines / chemical synthesis
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Piperidines / chemistry
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Piperidines / pharmacology
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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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Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
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TNF-Related Apoptosis-Inducing Ligand / pharmacology
Substances
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Amines
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Piperidines
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Protein Kinase Inhibitors
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Pyrimidines
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TNF-Related Apoptosis-Inducing Ligand
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Proto-Oncogene Proteins c-akt
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Caspase 3