79669-90-2Relevant articles and documents
Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 1
Ohshima,Takami,Sato,Obase,Miki,Ishii,Karasawa,Kubo
, p. 3394 - 3402 (2007/10/02)
A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were synthesized. The compounds were tested for their antagonizing effects on guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed. (±)-11-[[2-[(Styrylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acid (41) and (±)-11-[[2- [(phenylsulfonyl)amino]ethyl]thio]-6,11-dihydrodibenz[b,e]thiepin-2- carboxylic acid (4af) were the most promising compounds with K(i) values of 6.5 ± 0.29 and 3.7 ± 0.31 nM, respectively, for the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619-induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was resolved into its optically active form. The (-)-isomer was 60-fold more potent than the (+)- isomer in the TXA2/PGH2 receptor binding assay. Some compounds tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2 synthase inhibitory effects.
TRICYCLIC COMPOUNDS
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, (2008/06/13)
Novel tricyclic compound represented by formula STR1 possess a TXA. sub.2 biosynthesis inhibiting activity and/or a TXA 2 receptor antagonizing activity, and are expected to have preventive and therapeutic effects on ischemic diseases, cerebro-vascular diseases, etc.
A new series of antiallergic agents. I. Synthesis and activity of 11-(2-aminoethyl)thio-6,11-dihydrodibenz[b,e]oxepin derivatives
Ohshima,Kumazawa,Takizawa,Harakawa,Sato,Obase,Oiji,Ishii,Ishii,Ohmori
, p. 2724 - 2728 (2007/10/02)
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.
Tricyclic compounds
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, (2008/06/13)
Novel tricyclic compounds having a TXA2 -antagonizing activity represented by formula (I): STR1 which strongly antagonize an action of thromboxane A2 and are expected to have preventive and therapeutic effects on ischemica diseases, cerebro-vascular diseases, etc.
Dibenz[b,e]oxepin compounds
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, (2008/06/13)
Novel dibenz[b,e]oxepin derivatives are employed in the treatment and control of allergic conditions such as allergic asthma.