Abstract:
:In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2B and A3 adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA1 and hA2A adenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A1/A2A antagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA1 Ki = 10.2 nM; hA2A Ki = 4.72 nM) and behaved as a potent A1/A2A antagonist/inverse agonist (hA1 IC50 = 13.4 nM; hA2A IC50 = 5.34 nM).
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Varano F,Catarzi D,Falsini M,Vincenzi F,Pasquini S,Varani K,Colotta Vdoi
10.1016/j.bmc.2018.05.048subject
Has Abstractpub_date
2018-07-23 00:00:00pages
3688-3695issue
12eissn
0968-0896issn
1464-3391pii
S0968-0896(18)30541-8journal_volume
26pub_type
杂志文章abstract::A growing number of proteins are known to exert their regulatory or biological functions via RNA binding. In some cases genetic interactions allow us to infer candidate targets for RNA directed regulation, but in many other cases identification of potential regulatory targets is problematic. We have developed an in vi...
journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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更新日期:2016-03-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2016-07-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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更新日期:2006-03-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2004.08.009
更新日期:2004-11-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2015-07-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)82075-1
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2006-03-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.09.045
更新日期:2009-11-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.09.016
更新日期:2009-11-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/s0968-0896(97)00146-6
更新日期:1997-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2011.01.050
更新日期:2011-03-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2010-07-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2013-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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更新日期:2017-02-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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