Abstract
In this study, we have investigated the roles of substituents on the terminal phenyl ring at the C(4)-position of the quinazoline core to complete the structure-activity relationships (SARs) of our NF-kappa B activation inhibitors. Among them, compound 12j afforded highly potent inhibitory activity toward NF-kappa B transcriptional activation with IC(50) value of 2 nM, along with an excellent in vivo efficacy by reducing the edema formation seen in carrageenin-induced inflammation of the rat hind paw.
MeSH terms
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Aminoquinolines / chemistry*
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Aminoquinolines / pharmacology
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Carrageenan
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Edema / chemically induced
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Edema / drug therapy
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Inflammation / chemically induced
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Inhibitory Concentration 50
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Quinazolines / chemistry*
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Quinazolines / pharmacology
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Rats
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Spleen / cytology
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Spleen / drug effects
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Spleen / growth & development
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Structure-Activity Relationship
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Transcriptional Activation / drug effects
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Tumor Necrosis Factor-alpha / metabolism
Substances
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6-amino-4-(4-n-pentyloxy)phenethylaminoquinazoline
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Aminoquinolines
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Anti-Inflammatory Agents, Non-Steroidal
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NF-kappa B
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Quinazolines
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Tumor Necrosis Factor-alpha
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6-aminoquinoline
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Carrageenan