Abstract
A series of phenothiazine carboxylic acid derivatives, having 6-amino-pyrimidine-2,4(1H,3H)-dione moiety via a appropriate linker, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice and bioavailability in rats. Finally, promising compounds were examined for their anti-inflammatory potential in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, phenothiazineacetic acid compound 27 showed both histamine H(1)-receptor antagonistic activity and anti-inflammatory activity in vivo model.
MeSH terms
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Administration, Oral
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Caco-2 Cells
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / chemistry*
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Carboxylic Acids / pharmacology
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Cell Line, Tumor
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Histamine H1 Antagonists / chemical synthesis*
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Histamine H1 Antagonists / chemistry
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Histamine H1 Antagonists / pharmacology
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Humans
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Mice
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Phenothiazines / chemical synthesis
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Phenothiazines / chemistry*
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Pyrimidinones / chemical synthesis
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Pyrimidinones / chemistry*
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Rats
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Receptors, Histamine H1 / metabolism*
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Carboxylic Acids
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Histamine H1 Antagonists
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Phenothiazines
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Pyrimidinones
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Receptors, Histamine H1