Linked Life Data

8627605

Source:http://linkedlifedata.com/resource/pubmed/id/8627605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1996-6-25
pubmed:abstractText
The presence of a molecular scaffold to orient a basic group is important for potent and selective kappa opioid antagonist selectivity. An attempt to determine how the geometry of the scaffold affects this selectivity has led to the synthesis of a bivalent ligand (5) whose linker constrains the N17' basic nitrogen (the "address") to a position that is 6.5 A from N17' in the kappa antagonist norBNI (1) when these molecules are superimposed. The fact that compound 5 was found to be a highly selective and potent mu-selective antagonist supports the idea that the position of N17' in 5 precludes effective ion pairing with the nonconserved residue Glu297 on outer loop 3 of the kappa opioid receptor. The high mu receptor binding affinity and in vitro pharmacological selectivity of 5 coupled with its presumed low central nervous system bioavailability suggest that it may be a useful antagonist for the investigation of peripheral mu opioid receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1816-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Opioid antagonist activity of naltrexone-derived bivalent ligands: importance of a properly oriented molecular scaffold to guide "address" recognition at kappa opioid receptors.
pubmed:affiliation
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.