Linked Life Data

11703148

Source:http://linkedlifedata.com/resource/pubmed/id/11703148

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-11-12
pubmed:abstractText
A 3042 compound screening library was synthesized using a combination of two solid-phase technologies: REM resin methodology and Lewis acid promoted aminolysis. The exclusivity and structural diversity of the library were enhanced by using a highly divergent synthetic strategy involving 13 different scaffolds (9 of which were custom-made), five different types of resin-bound phenol derivatization chemistry (Mitsunobu, Suzuki, acylation, sulfonylation, and carbamoylation), and three different cleavage strategies (Hofmann elimination, AlCl(3)-promoted aminolysis, base-promoted esterolysis). This is the first example of a solid-phase Suzuki coupling involving a resin-bound aryl triflate being used for library synthesis. Computational analysis suggested that the compounds are likely to have favorable properties for CNS penetration. Analysis of the library by HPLC and MS suggested at least 90% of the sampled members were present in an average purity of approximately 70%. Encouragingly, hits have been identified from high-throughput screening of this library, such as compound 6, which has an affinity of 1.02 microM for the GlyT(2) transporter.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1520-4766
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
534-41
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:articleTitle
Design and synthesis of a maximally diverse and druglike screening library using REM resin methodology.
pubmed:affiliation
Lead Discovery Chemistry, Organon Laboratories Ltd., Newhouse, ML1 5SH, Scotland, U.K.
pubmed:publicationType
Journal Article