Linked Life Data

12150879

Source:http://linkedlifedata.com/resource/pubmed/id/12150879

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-8-1
pubmed:abstractText
Enantiomeric analogues of 5-(3-hydroxyphenyl)morphan ligands were synthesized and evaluated because of our unexpected finding that opioid antagonists can be obtained in the 5-phenylmorphan series of opioids without sterically hindering the rotation of the phenolic ring. We determined the opioid receptor binding affinity of these new analogues, as well as the efficacy of the more interesting ligands. One of the new compounds [(1R,5S)-(-)-3-[2-(3'-phenylpropyl)-2-azabicyclo[3.3.1]non-5-yl]-phenol, 15] was found to have half of the efficacy of naloxone, a potent opioid antagonist, in the [(35)S]GTPgammaS assay, and two others (1R,5S)-(-)-3-[2-(4'-phenylbutyl)-2-azabicyclo[3.3.1]non-5-yl]-phenol, 17, and (1R,5S,1'S)-(+)-3-[2-(1'-methyl-2'-phenylethyl)-2-azabicyclo[3.3.1]non-5-yl]-phenol, 26, acted as moderately potent opioid antagonists. X-ray crystallographic structure data were obtained on three compounds. Two of them had three chiral centers; 25 [(1R,5S,1'R)-(-)-3-[2-(1'-methyl-2'-phenylethyl)-2-azabicyclo[3.3.1]non-5-yl]-phenol] was determined to have the 1R,5S,1'R configuration, and 26 the 1R,5S,1'S configuration. Since (1S,5R)-(+)-2-bromo-5-[2-(2'-phenylethyl)-2-azabicyclo[3.3.1]non-5-yl]-phenol (32) was a position isomer of (1S,5R)-(+)-4-bromo-3-[2-(2'-phenylethyl)-2-azabicyclo[3.3.1]non-5-yl]-phenol (30), and both showed the same 1H NMR spectrum, the structure of 32 was unequivocally determined by X-ray structure analysis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3319-29
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Probes for narcotic receptor mediated phenomena. Part 28: new opioid antagonists from enantiomeric analogues of 5-(3-hydroxyphenyl)-N-phenylethylmorphan.
pubmed:affiliation
Laboratory of Medicinal Chemistry, Building 8, Room B1-23, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0815, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.