Abstract
A novel series of 2-aminothiazole-oxazoles was designed and synthesized as part of efforts to develop potent phosphoinositide 3-kinase γ (PI3Kγ) inhibitors. The modification of a high-throughput screening hit, compound 1, resulted in the identification of compounds 10 and 15, which displayed potent inhibitory activities in enzyme-based and cell-based assays.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Class Ib Phosphatidylinositol 3-Kinase / metabolism
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Discovery*
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High-Throughput Screening Assays
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Macrophages / drug effects
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Macrophages / enzymology
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Macrophages / metabolism
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Mice
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Models, Molecular
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Molecular Structure
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Oxazoles / chemistry
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Oxazoles / pharmacology*
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Phosphoinositide-3 Kinase Inhibitors*
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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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Structure-Activity Relationship
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Thiazoles / chemistry
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Thiazoles / pharmacology*
Substances
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Oxazoles
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Thiazoles
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2-aminothiazole
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Class Ib Phosphatidylinositol 3-Kinase
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Pik3cg protein, mouse