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Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors |
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| Authors: | Isao Sakurada Toshiya Endo Katsuyoshi Hikita Tomokazu Hirabayashi Yoshitaka Hosaka Yutaka Kato Yoshitaka Maeda Shigeki Matsumoto Takashi Mizuno Hiroshi Nagasue Teruyuki Nishimura Shunsuke Shimada Mikihiko Shinozaki Keiko Taguchi Katsutoshi Takeuchi Tooru Yokoyama Alan Hruza Paul Reichert Shoji Furusako |
| Institution: | 1. Discovery Research, Mochida Pharmaceutical Co. Ltd., 722 Uenohara, Jimba, Gotemba, Shizuoka 412-8524, Japan;2. Department of Structural Chemistry, Merck Research Laboratories, Merck and Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;3. Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA |
| Abstract: | Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated. |
| Keywords: | Factor IXa inhibitor Anticoagulant Aminobenzisoxazole Azabicyclic ring Structure based drug design |
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