Abstract
New methods for the preparation of multi-functionalized-6,11-dihydrodibenz[b,e]oxepins were developed. The structural requirements of KW-4994 (1), a promising orally active antiallergic agent, were defined. A carboxyl group at C-2 was critical for enhanced antiallergic activity of 1. The introduction of bromine atom at C-9 of 1 could elongate the duration of the action of the parent. Antiplatelet activity, a new pharmacological property of this series of compounds, was observed in one of the derivatives of 1.
MeSH terms
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Animals
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Benzoxepins / chemical synthesis*
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Benzoxepins / pharmacology
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Benzoxepins / therapeutic use
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Corpus Striatum / metabolism
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Guinea Pigs
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Histamine H1 Antagonists / chemical synthesis*
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Histamine H1 Antagonists / pharmacology
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Histamine H1 Antagonists / therapeutic use
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Hypersensitivity, Delayed / drug therapy
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Male
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Rats
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Rats, Inbred Strains
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Receptors, Cholinergic / drug effects
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Receptors, Cholinergic / metabolism
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Structure-Activity Relationship
Substances
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Benzoxepins
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Histamine H1 Antagonists
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Receptors, Cholinergic