Linked Life Data

19243173

Source:http://linkedlifedata.com/resource/pubmed/id/19243173

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-4-2
pubmed:abstractText
A series of 6,8-diazabicyclo[3.2.2]nonane derivatives bearing two aromatic moieties was prepared, the affinity toward sigma(1) and sigma(2) receptors was investigated, and the growth inhibition of six human tumor cell lines was determined. The enantiopure bicyclic ketones 5a ((+)-(1S,5S)-6-allyl-8-(4-methoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane-2,7,9-trione) and 5b ((+)-(1S,5S)-6-allyl-8-(2,4-dimethoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane-2,7,9-trione) as well as their enantiomers ent-5a and ent-5b served as chiral building blocks, which were derived from (S)- and (R)-glutamate, respectively. Structure-affinity relationships revealed that 11a (K(i) = 154 nM), ent-11a (K(i) = 91 nM), and ent-17a (K(i) = 104 nM) are the most potent sigma(1) ligands. High sigma(2) affinity was achieved with 17b (K(i) = 159 nM) and 8b (K(i) = 400 nM). The bicyclic sigma ligands showed a selective growth inhibition of the small cell lung cancer cell line A-427 with the benzyl ethers 11 and the benzylidene derivatives 17 being the most potent compounds. 11a has a cytotoxic potency (IC(50) = 0.92 muM), which exceeds the activity of cisplatin and interacts considerably with both sigma(1) and sigma(2) receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2126-37
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Dancing of the second aromatic residue around the 6,8-diazabicyclo[3.2.2]nonane framework: influence on sigma receptor affinity and cytotoxicity.
pubmed:affiliation
Institut fur Pharmazeutische und Medizinische Chemie der Westfalischen Wilhelms-Universitat Munster, Munster, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't