Abstract
A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure-activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC50 values between 33 and 83nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemistry*
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Anti-Inflammatory Agents / metabolism
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Anti-Inflammatory Agents / pharmacokinetics
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Benzoxazoles / chemistry*
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Boron Compounds / chemistry*
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Boron Compounds / metabolism
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Boron Compounds / pharmacokinetics
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / metabolism*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
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Half-Life
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Humans
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / metabolism
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / metabolism
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Kinetics
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Leukocytes, Mononuclear / drug effects
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Lipopolysaccharides / toxicity
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Mice
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Protein Binding
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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6-(4-(aminomethyl)-2-chlorophenoxyl)benzo(c)(1,2)oxaborol-1(3H)-ol
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Anti-Inflammatory Agents
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Benzoxazoles
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Boron Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha