- 著者
- 大島 悦男 佐藤 秀幸 小場瀬 宏之 内村 達雄 桑原 隆 小林 智
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.40, no.9, pp.2552-2554, 1992-09-25 (Released:2008-03-31)
- 参考文献数
- 8
- 被引用文献数
- 2 6
(Z)-11-[3-(Dimethlamino)propylidene]-2-(methoxycarbonyl)methyl-6, 11-dihydrodibenz[b, e]oxepin-9-acrylic acid (5) was prepared for application to the radiommunoassay of KW-4679 (1, (Z)-11-[3-(dimethylamino)propylidene]-6, 11-dihydrodibenz[b, e]oxepin-2-acetic acid hydrochloride). The acrylic acid moiety in the 9-position of 5 was employed for coupling with an amino group of bovine serum albumin (BSA) to provide 17. Subsequently, the conjugate 17 was treated with aquenus NaOH to hydrolyze the terminal methoxycarbonyl group in the 2-position of the BSA conjugated 5. Antiserum raised against the antigenic BSA-conjugate 4 finally obtained was specific for 1.
- 著者
- 熊沢 利昭 大島 悦男 原川 洋行 佐藤 秀幸 小場瀬 宏之 生地 由昌 石井 昭男 石井 秀衛 大森 健守
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.39, no.10, pp.2729-2733, 1991-10-25 (Released:2008-03-31)
- 参考文献数
- 14
- 被引用文献数
- 2 4
New methods for the preparation of multi-functionallized-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 of 1. The introduction of bromine atom at C-9 of 1 could elongate the duration of the action of the parent. Antiplatelet acetivity, a new pharmacological property of this series of compounds, was observed in one of the derivatives of 1.
- 著者
- 大島 悦男 熊沢 利昭 滝沢 博 原川 洋行 佐藤 秀幸 小場瀬 宏之 生地 由昌 石井 昭男 石井 秀衛 大森 健守
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.39, no.10, pp.2724-2728, 1991-10-25 (Released:2008-03-31)
- 参考文献数
- 28
- 被引用文献数
- 2 3
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-carboxylic acid hydrochloride, was the most potent in the rat passive cutaneous anaphylaxis test (ED50=0.92 mg/lg 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 (Ki=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.