Linked Life Data

20307065

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

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pubmed-article:20307065pubmed:abstractTextAmong 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.lld:pubmed
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pubmed-article:20307065pubmed:articleTitleThe 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.lld:pubmed
pubmed-article:20307065pubmed:affiliationDepartment of Pharmacy, National University of Singapore, 3 Science Drive 2, Block S15, no. 05-PI-03, Singapore 117543.lld:pubmed
pubmed-article:20307065pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20307065pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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