A new series of antiallergic agents. I. Synthesis and activity of 11-(2-aminoethyl)thio-6,11-dihydrodibenz[b,e]oxepin derivatives

Article abstract of DOI:10.1248/cpb.39.2724

A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin derivatives was synthesized and evaluated for antiallergic activity. Convenient methods for the preparation of sulfides from alcohols were developed. Structure-activity relationships are described. Compound 7, 11-[2-(dimethylamino)ethyl]thio-6,11-dihydrodibenz[b,e]oxepin-2-carboxy lic acid hydrochloride, was the most potent in the rat passive cutaneous anaphylaxis test (ED₅₀ = 0.92 mg/kg p.o.). It had a potent inhibitory effect on anaphylactic bronchoconstriction in guinea pigs (ED₅₀ = 0.029 mg/kg p.o.) and H₁ receptor antagonistic effect (K(i) = 14 nM) with few central nervous system side effects. Additionally, an antagonistic effect against prostagrandin D₂-induced contraction of isolated guinea pig trachea (pA₂ = 5.73) was an attractive mechanism of action of the new antiallergic agent. Compound 7 was selected for further evaluation as KW-4994.

Full text of DOI:10.1248/cpb.39.2724

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NII-Electronic Library Service

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NII-Electronic Library Service