Linked Life Data

20307065

Source:http://linkedlifedata.com/resource/pubmed/id/20307065

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-4-15
pubmed:abstractText
Among the heterocyclic structures identified as potent human A(3) (hA(3)) adenosine receptor's antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C(2)-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines showed affinity at the hA(3) receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, K(i) hA(3) = 0.108 nM; hA(1)/hA(3) = 5200; hA(2A)/hA(3) = 7200), in comparison to the C(2)-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A(3) receptor derived from the crystallographic structure of human A(2A) receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes.
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
22
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3361-75
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20307065-Acetamides, pubmed-meshheading:20307065-Adenosine A1 Receptor Antagonists, pubmed-meshheading:20307065-Adenosine A2 Receptor Antagonists, pubmed-meshheading:20307065-Adenosine A3 Receptor Antagonists, pubmed-meshheading:20307065-Adenylate Cyclase, pubmed-meshheading:20307065-Animals, pubmed-meshheading:20307065-CHO Cells, pubmed-meshheading:20307065-Cricetinae, pubmed-meshheading:20307065-Cricetulus, pubmed-meshheading:20307065-Furans, pubmed-meshheading:20307065-Heterocyclic Compounds, 3-Ring, pubmed-meshheading:20307065-Humans, pubmed-meshheading:20307065-Models, Molecular, pubmed-meshheading:20307065-Pyrazoles, pubmed-meshheading:20307065-Pyrimidines, pubmed-meshheading:20307065-Radioligand Assay, pubmed-meshheading:20307065-Structure-Activity Relationship, pubmed-meshheading:20307065-Triazoles
pubmed:year
2010
pubmed:articleTitle
The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA(3) adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition.
pubmed:affiliation
Department of Pharmacy, National University of Singapore, 3 Science Drive 2, Block S15, no. 05-PI-03, Singapore 117543.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't