Abstract
The design, synthesis, and the biological evaluation of 2-benzamido-pyrimidines as novel IKK inhibitors are described. By optimization of the lead compound 3, compounds 16 and 24 are identified as good inhibitors of IKK2 with IC(50) values of 40 and 25 nM, respectively. Compound 16 also demonstrated significant in vivo activity in an acute model of cytokine release.
MeSH terms
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Chemistry, Pharmaceutical / methods*
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Drug Design
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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HeLa Cells
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Humans
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I-kappa B Kinase / antagonists & inhibitors*
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Inhibitory Concentration 50
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Models, Chemical
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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
Substances
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Cytokines
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Enzyme Inhibitors
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Pyrimidines
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I-kappa B Kinase