Abstract
This paper describes the rapid assembly of four different classes of potent Akt inhibitors from a common intermediate. Among them, a pyridopyrimidine series displayed the best intrinsic and cell potency against Akt1 and Akt2. This series also showed a promising pharmacokinetic profile and excellent selectivity over other closely related kinases.
MeSH terms
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Allosteric Site*
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Animals
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Apoptosis / drug effects
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Caspases / metabolism
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Dogs
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Female
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Humans
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Male
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Metabolic Clearance Rate
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Molecular Structure
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism
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Phosphorylation / drug effects
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / metabolism
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
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Proto-Oncogene Proteins c-akt / metabolism
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Pyridines / chemistry*
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Pyrimidines / chemistry*
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Structure-Activity Relationship
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TNF-Related Apoptosis-Inducing Ligand / pharmacology
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Tumor Cells, Cultured
Substances
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Protein Kinase Inhibitors
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Pyridines
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Pyrimidines
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Proto-Oncogene Proteins c-akt
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Caspases