Discovery of 7-(Prolinol-N-yl)-2-phenylamino-thiazolo[5,4-d]pyrimidines as Novel Non-Nucleoside Partial Agonists for the A(2A) Adenosine Receptor: Prediction from Molecular Modeling
2016 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 59, no 12, 5922-5928 p.Article in journal (Refereed) PublishedText
We describe the identification of 7-(prolinol-N-yl)-2-phenylamino-thiazolo[5,4-d]pyrimidines as a novel chemotype of non-nucleoside partial agonists for the A(2A) adenosine receptor (A(2A)AR). Molecular-modeling indicated that the (S)-2-hydroxymethylene-pyrrolidine could mimic the interactions of agonists' ribose, suggesting that this class of compounds could have agonistic properties. This was confirmed by functional assays on the A(2A)AR, where their efficacy could be associated with the presence of the 2-hydroxymethylene moiety. Additionally, the best compound displays promising affinity, selectivity profile, and physicochemical properties.
Place, publisher, year, edition, pages
2016. Vol. 59, no 12, 5922-5928 p.
IdentifiersURN: urn:nbn:se:uu:diva-299890DOI: 10.1021/acs.jmedchem.6b00552ISI: 000378662900027PubMedID: 27227326OAI: oai:DiVA.org:uu-299890DiVA: diva2:950521