- 著者
- Tetsuji Noguchi Naoki Tanaka Toyoki Nishimata Riki Goto Miho Hayakawa Atsuhiro Sugidachi Taketoshi Ogawa Yoichi Niitsu Fumitoshi Asai Tomoko Ishizuka Koichi Fujimoto
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.57, no.1, pp.22-33, 2009-01-01 (Released:2009-01-01)
- 参考文献数
- 25
- 被引用文献数
- 10 13
To develop a novel and effective anticoagulant with potent and selective factor Xa (FXa) inhibitory activity, a new series of cinnamyl derivatives with enhanced lipophilicity and prodrug forms were synthesized and their biological activities were evaluated. As a result, we found that cinnamyl derivative (N-{4-[1-(acetimidoyl)piperidin-4-yloxy]-3-carbamoylphenyl}-N-[(Z)-3-(3-amidinophenyl)-2-fluoro-2-propenyl]sulfamoyl)acetic acid dihydrochloride (26d, R-142086) with a fluorine atom on the double bond exhibited potent anticoagulant activity and no mutagenic potential. Moreover, orally administered R-142086 exhibited potent anti-FXa activity and anticoagulant activity in dogs.
- 著者
- Naoki TANAKA Riki GOTO Rie ITO Miho HAYAKAWA Taketoshi OGAWA Koichi FUJIMOTO
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.46, no.4, pp.639-646, 1998-04-15 (Released:2008-03-31)
- 参考文献数
- 14
- 被引用文献数
- 2 2
A series of [2-(ω-phenylalkyl)phenoxy]alkylamines was synthesized and their 5-hydroxytryptamine2 (5-HT2) and/or dopamine2 (D2) receptor antagonistic activities were examined in vitro. [2-(4-Phenylbutyl)phenoxy]alkylamines showed strong inhibition of both 5-HT2 and D2 receptors. It particular, [2-(4-phenylbutyl)phenoxy]-methylpiperidine derivatives, 10b, 10i and 10q, exhbited potent inhibition. The structure-activity relationships in this series of compounds are discussed.
1 0 0 0 OA [2-(ω-Phenylalkyl)phenoxy]alkylamines II : Synthesis and Selective Serotonin-2-Receptor Binding
- 著者
- Naoki TANAKA Riki GOTO Miho HAYAKAWA Atsuhiro SUGIDACHI Taketoshi OGAWA Fumitoshi ASAI Koichi FUJIMOTO
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.48, no.2, pp.245-255, 2000-02-01 (Released:2008-03-31)
- 参考文献数
- 26
- 被引用文献数
- 4 5
A series of [2-(ω-phenylalkyl)phenoxy]alkylamines was synthesized and thir receptor binding affinity was examined in vitro. These compounds showed an affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors. [2-(2-phenylethyl)phenoxy]alkylamine derivatives with a pyrrolidine or piperidine moiety in the structure showed higher affinity for 5-HT2 receptors but lower affinity for D2 receptors. Among these compounds, (S)-2-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]1-methylpyrrolidine, (S)-27, exhibited the most potent and selective affinity for 5-HT2 receptors. Furthermore, (S)-27 was effective in inhibiting 5-HT-induced vasoconstriction in vitro and platelet aggregation both in vitro and ex vivo.