論文

査読有り
2010年1月

Design and Synthesis of Peptidomimetic Factor VIIa Inhibitors

CHEMICAL & PHARMACEUTICAL BULLETIN
  • 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
  • 全て表示

58
1
開始ページ
38
終了ページ
44
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/cpb.58.38
出版者・発行元
PHARMACEUTICAL SOC JAPAN

Selective factor Vila-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.

リンク情報
DOI
https://doi.org/10.1248/cpb.58.38
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20045964
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000273168400008&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=74749090533&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=74749090533&origin=inward
ID情報
  • DOI : 10.1248/cpb.58.38
  • ISSN : 0009-2363
  • eISSN : 1347-5223
  • PubMed ID : 20045964
  • SCOPUS ID : 74749090533
  • Web of Science ID : WOS:000273168400008

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