Linked Life Data

16420046

Source:http://linkedlifedata.com/resource/pubmed/id/16420046

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-19
pubmed:abstractText
Transmissible spongiform encephalopathies (TSEs) or prion diseases are a family of invariably fatal neurodegenerative disorders, and there are no effective therapeutics currently available. In this paper, we report on the design, synthesis, and screening of a series of pyridine dicarbonitriles as potential novel prion disease therapeutics. A virtual reaction-based library of 1050 compounds was constructed. Docking and evaluation using GOLD scores assisted the initial selection of compounds for synthesis. The selection was augmented with further compounds to increase structural diversity. A total of 45 compounds were synthesized via a one-pot three-component coupling reaction. The mechanism of the three-component coupling reaction was investigated, and it was discovered that chemical oxidation is required for the last step, forming the pyridine ring (aromatization). A total of 19 compounds were identified as binders to one or more forms of prion protein by in vitro screening using surface plasmon resonance (SPR). A selection of compounds were investigated for activity in cells, resulting in the discovery of a new inhibitor of PrP(Sc) formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
607-15
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Library design, synthesis, and screening: pyridine dicarbonitriles as potential prion disease therapeutics.
pubmed:affiliation
Department of Chemistry, The University of Sheffield, Sheffield S3 7HF, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't