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Masahiko Uchida

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Publication

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Bioorganic & Medicinal Chemistry Letters | 2008

Orally active factor Xa inhibitors: investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy.

Masahiko Uchida; Kosuke Okazaki; Harunobu Mukaiyama; Hidetoshi Isawa; Hiroaki Kobayashi; Hiroaki Shiohara; Hideyuki Muranaka; Yuichiro Kai; Norihiko Kikuchi; Hideki Takeuchi; Kenji Yokoyama; Eiichi Tsuji; Tomonaga Ozawa; Yuji Hoyano; Takashi Koizumi; Keiko Misawa; Kiyoto Hara; Shigeru Nakano; Yasuoki Murakami; Hiroaki Okuno

A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development.

Archive | 1998

3-amidinoaniline derivatives, activated blood coagulation factor x inhibitors, and intermediates for producing both

Satoshi Akahane; Masahiko Uchida; Hideotoshi Isawa; Norihiko Kikuchi; Tomonaga Ozawa; Hiroaki Kobayashi; Yuichiro Kai; Kenji Akahane

Archive | 2001

5-amidino-2-hydroxybenzenesulfonamide derivatives, pharmaceutical compositions containing the same and intermediates for their preparation

Kosuke Okazaki; Masahiko Uchida; Harunobu Mukaiyama; Hiroaki Kobayashi; Yuichiro Kai; Hideki Takeuchi; Kenji Yokoyama; Yoshihiro Terao; Yuji Hoyano; Hiroaki Shiohara; Norihiko Kikuchi

Archive | 2002

5-amidino-2-hydroxybenzenesulfonamide derivatives, medicinal compositions containing the same, medicinal use thereof and intermediates in the production thereof

Masahiko Uchida; Hiroaki Kobayashi; Yuichiro Kai; Kenji Yokoyama; Yoshihiro Terao; Hideyuki Muranaka

Archive | 2000

3-amidinobenzenesulfonamide derivatives, medicinal compositions containing the same and intermediates in the production thereof

Satoshi Akahane; Masahiko Uchida; Hidetoshi Isawa; Norihiko Kikuchi; Yuichiro Kai; Kiyoto Hara; Toshiki Honma

Archive | 2002

5-amidino-n-(2-aminophenethyl)-n-hydroxy-benzenesulffonamide derivative, medical composition containing the same, pharmaceutical use thereof and intermediate therefor

Kosuke Okazaki; Masahiko Uchida; Hiroaki Kobayashi; Yuichiro Kai; Hideki Takeuchi; Kenji Yokoyama; Yoshihiro Terao; Ritsu Suzuki

Journal of Toxicological Sciences | 2003

Characteristics of the hemostatic action of KFA-1411, an inhibitor of coagulation factor Xa (FXa), in humans and various animals

Kiyoto Hara; Toshiki Honma; Akane Matsuzawa; Atsushi Matsuzawa; Masahiko Uchida; Takashi Koizumi; Satoshi Akahane; Masami Kojima

Journal of Health Science | 2003

Evaluation of a New Blood Coagulation Factor Xa Inhibitor, KFA-1411, as an Anticoagulant in a Cynomolgus Monkey Hemodialysis Model: Parameters Suitable for Monitoring Anticoagulant Activities

Kiyoto Hara; Toshiki Honma; Yuji Hoyano; Takashi Koizumi; Masahiko Uchida; Satoshi Akahane; Masami Kojima; Masuo Akahane

Archive | 2002

5-amidino-n-(2-aminophenethyl)-hydroxybenzenesulfonamide derivative, medicinal composition containing the same, and intermediate therefor

Kosuke Okazaki; Masahiko Uchida; Hiroaki Kobayashi; Yuichiro Kai; Hideki Takeuchi; Kenji Yokoyama; Yoshihiro Terao; Ritsu Suzuki

Archive | 2001

5-amidino-2-hydroxybenzolsulfonamidderivate pharmaceutical compositions containing these compounds, and intermediates for their preparation

Kosuke Okazaki; Masahiko Uchida; Harunobu Mukaiyama; Hiroaki Kobayashi; Yuichiro Kai; Hideki Takeuchi; Kenji Yokoyama; Yoshihiro Terao; Yuji Hoyano; Hiroaki Shiohara; Norihiko Kikuchi

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Hiroaki Kobayashi

Shinshu University

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Kosuke Okazaki

Shinshu University

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Satoshi Akahane

Shinshu University

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Masami Kojima

Fukuoka Dental College

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Akane Matsuzawa

Shinshu University

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Atsushi Matsuzawa

University of Tokyo

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Hiroaki Okuno

Toho University

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Masuo Akahane

Saitama Medical University

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Yasuoki Murakami

Chiba Institute of Science

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