2010年1月
Design and Synthesis of Peptidomimetic Factor VIIa Inhibitors
CHEMICAL & PHARMACEUTICAL BULLETIN
- 巻
- 58
- 号
- 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