Linked Life Data

18248994

Source:http://linkedlifedata.com/resource/pubmed/id/18248994

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-3-17
pubmed:abstractText
Previous work on human NK(1) antagonists in which the core of the structure is a substituted pyrrolidine has been disclosed. These compounds showed good binding affinity and functional IP activity, however, many did not exhibit the necessary brain penetration for good in vivo activity. The discovery and preparation of a novel 5,5-fused pyrrolidine core is presented in this paper. This scaffold maintains the excellent binding affinity and functional IP activity of the previously reported compounds, but also exhibits excellent brain penetration as observed in a gerbil foot-tapping assay. The determination of the core structural stereochemistry, which eventually led to the final synthesis of a single active diastereomer, is described.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2156-70
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Fused bicyclic pyrrolizinones as new scaffolds for human NK1 antagonists.
pubmed:affiliation
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't