- 著者
- Kazutaka Tachibana Ikuhiro Imaoka Takuya Shiraishi Hitoshi Yoshino Mitsuaki Nakamura Masateru Ohta Hiromitsu Kawata Kenji Taniguchi Nobuyuki Ishikura Toshiaki Tsunenari Hidemi Saito Masahiro Nagamuta Toshito Nakagawa Kenji Takanashi Etsuro Onuma Haruhiko Sato
- 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.10, pp.1178, 2009-10-01 (Released:2009-10-03)
- 著者
- Takuya Shiraishi Shojiro Kadono Masayuki Haramura Hirofumi Kodama Yoshiyuki Ono Hitoshi Iikura Tohru Esaki Takaki Koga Kunihiro Hattori Yoshiaki Watanabe Akihisa Sakamoto Kazutaka Yoshihashi Takehisa Kitazawa Keiko Esaki Masateru Ohta Haruhiko Sato Toshiro Kozono
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.58, no.1, pp.38-44, 2010-01-01 (Released:2010-01-01)
- 参考文献数
- 29
- 被引用文献数
- 1
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. In previous reports, we described a S3 subsite found in the X-ray crystal structure of compound 2 that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure information and with the aim of improving the inhibition activity for FVIIa/TF and selectivity against other serine proteases, we synthesized derivatives by introducing substituents at position 5 of the indole ring of compound 2. Among them, compound 16 showed high selectivity against other serine proteases. Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray structure analysis revealed that compound 16 improved selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.
- 著者
- Kazutaka Tachibana Ikuhiro Imaoka Takuya Shiraishi Hitoshi Yoshino Mitsuaki Nakamura Masateru Ohta Hiromitsu Kawata Kenji Taniguchi Nobuyuki Ishikura Toshiaki Tsunenari Hidemi Saito Masahiro Nagamuta Toshito Nakagawa Kenji Takanashi Etsuro Onuma Haruhiko Sato
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.56, no.11, pp.1555-1561, 2008-11-01 (Released:2008-11-01)
- 参考文献数
- 21
- 被引用文献数
- 14 20
The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC50=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED50=7 mg/kg).