Structural investigation on thiazolo[5,4-d]pyrimidines to obtain dual-acting blockers of CD73 and adenosine A receptor as potential antitumor agents.

Adenosine pathway, including its generating enzyme (CD73) and its receptors represents a key target for cancer immunotherapy. Here we aimed to search for novel compounds able to co-target the CD73 and the A adenosine receptor (A AR) as dual-blockers of adenosine generation and activity. The design project was to combine in the same molecule the thiazolo[5,4-d]pyrimidine core, an essential pharmacophoric feature to block the A AR, with a benzenesulfonamide group which is a characteristic group of CD73 inhibitors. Most of the reported compounds resulted in inverse agonists of the human (h) A AR endowed with high affinity, selectivity and potency. However they were weak inhibitors of CD73 enzyme. Nevertheless, this study can be considered as a starting point to develop more active compounds.