- 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.