rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
2
|
pubmed:dateCreated |
2006-12-15
|
pubmed:abstractText |
Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-l-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the P1-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a K(i) value of 1.1nM.
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
0968-0896
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
15
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
827-38
|
pubmed:meshHeading |
pubmed-meshheading:17107807-Cyclopentanes,
pubmed-meshheading:17107807-Dicarboxylic Acids,
pubmed-meshheading:17107807-Indicators and Reagents,
pubmed-meshheading:17107807-Kinetics,
pubmed-meshheading:17107807-Magnetic Resonance Spectroscopy,
pubmed-meshheading:17107807-Models, Molecular,
pubmed-meshheading:17107807-Protease Inhibitors,
pubmed-meshheading:17107807-Stereoisomerism,
pubmed-meshheading:17107807-Structure-Activity Relationship,
pubmed-meshheading:17107807-Viral Nonstructural Proteins
|
pubmed:year |
2007
|
pubmed:articleTitle |
Synthesis of novel potent hepatitis C virus NS3 protease inhibitors: discovery of 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a N-acyl-L-hydroxyproline bioisostere.
|
pubmed:affiliation |
Department of Chemistry, Linköping University, S-581 83 Linköping, Sweden.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|