liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Potent Macrocyclic Inhibitors of the Hepatitis C Virus NS3 Protease Incorporating Cyclopentane and Cyclopentene Derived Scaffolds
Linköping University, The Department of Physics, Chemistry and Biology.
Show others and affiliations
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:liu:diva-13984OAI: oai:DiVA.org:liu-13984DiVA: diva2:22384
Available from: 2006-09-14 Created: 2006-09-14 Last updated: 2010-01-13
In thesis
1. Design and Synthesis of Serine and Aspartic Protease Inhibitors
Open this publication in new window or tab >>Design and Synthesis of Serine and Aspartic Protease Inhibitors
2006 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the design and synthesis of compounds that are

intended to inhibit serine and aspartic proteases. The first part of the text deals with preparation of inhibitors of the hepatitis C virus (HCV) NS3 serine protease. Hepatitis C is predominantly a chronic disease that afflicts about 170 million people worldwide. The NS3 protease, encoded by HCV, is essential for replication of the virus and has become one of the main targets when developing drugs to fight HCV. The inhibitors discussed here constitute surrogates for the widely used N-acyl-hydroxyproline isostere designated 4-hydroxy-cyclopentene. The stereochemistry of the 4-hydroxy-cyclopentene scaffold was determined by nuclear overhauser effect spectroscopy (NOESY) and the regiochemistry by heteronuclear multiple bond correlation (HMBC). The scaffold was decorated with different substituents to obtain both linear and macrocyclic HCV NS3 protease inhibitors that display low nanomolar activity. The second part of the thesis describes the design and synthesis of potential aspartic protease inhibitors. The hydroxyethylene motif was used as a noncleavable transition state isostere. The synthetic route yielded a pivotal intermediate with excellent stereochemical control, which was corroborated by NOESY experiments. This intermediate can be diversified with different substituents to furnish novel aspartic protease inhibitors.

Place, publisher, year, edition, pages
Institutionen för fysik, kemi och biologi, 2006. 51 p.
Series
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1264
Keyword
organic chemistry, organic synthesis, metathesis, HCV, NS3, protease, proline isosteres, inhibitor, aspartic protease inhibitors, hydroxyethylene
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-7372 (URN)9185523216 (ISBN)
Presentation
2006-09-29, Schrödinger (E324), Hus E, Campus Valla, Linköpings universitet, Linköping, 14:00 (English)
Opponent
Supervisors
Note

Report code: LIU-TEK-LIC-2006:45

Available from: 2006-09-14 Created: 2006-09-14 Last updated: 2017-12-14

Open Access in DiVA

No full text

By organisation
The Department of Physics, Chemistry and Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 59 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf