Piperazine- and Piperidine-Containing Thiazolo54-dpyrimidine Derivatives as New Potent and Selective Adenosine A2A Receptor Inverse Agonists

摘要

The therapeutic use of A adenosine receptor (AR) antagonists for the treatment of neurodegenerative disorders, such as Parkinson and Alzheimer diseases, is a very promising approach. Moreover, the potential therapeutic role of A AR antagonists to avoid both immunoescaping of tumor cells and tumor development is well documented. Herein, we report on the synthesis and biological evaluation of a new set of piperazine- and piperidine- containing 7-amino-2-(furan-2-yl)thiazolo[5,4- ]pyrimidine derivatives designed as human A AR antagonists/inverse agonists. Binding and potency data indicated that a good number of potent and selective hA AR inverse agonists were found. Amongst them, the 2-(furan-2-yl)- -(2-(4-phenylpiperazin-1-yl)ethyl)thiazolo[5,4- ]pyrimidine-5,7-diamine exhibited the highest A AR binding affinity (K = 8.62 nM) as well as inverse agonist potency (IC = 7.42 nM). In addition, bioinformatics prediction using the web tool SwissADME revealed that , , and possessed good drug-likeness profiles.