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

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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

Hiroyuki AKAMA Masayuki HARAMURA Akito TANAKA Toshio AKIMOTO Noriaki HIRAYAMA

出版者

(社)日本分析化学会

雑誌

Analytical Sciences: X-ray Structure Analysis Online (ISSN:13482238)

巻号頁・発行日

vol.20, pp.x29-x30, 2004 (Released:2005-02-18)

参考文献数

4

被引用文献数

2

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The title compound, C9H15N5O, is an antialopecia agent. The crystal belongs to space group P21 with cell dimensions a = 9.3799(5) , b = 8.3319(4), c = 12.9984(7)Å and β = 90.191(3)°. The final R value is 0.092. There are two crystallographically independent molecules in an asymmetric unit. They adopt significantly different conformations. The hybridization states of the nitrogen atoms in piperidine rings are markedly different in these molecules.