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

作者：Bharate Sandip B; Singh Baljinder; Kachler Sonja; Oliveira Ana; Kumar Vikas; Bharate Sonali S; Vishwakarma Ram A; Klotz Karl Norbert; de Teran Hugo Gutierrez

来源：Journal of Medicinal Chemistry, 2016, 59(12): 5922-5928.

DOI：10.1021/acs.jmedchem.6b00552

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.

• 出版日期2016-6-23