Synthesis and Studies of Potential Inhibitors of CD73 Based on a Triazole Scaffold

• Published in: European journal of organic chemistry 2022-06, Vol.2022 (21), p.n/a
• Main Authors: Grosjean, Félix, Cros‐Perrial, Emeline, Braka, Abdenour, Uttaro, Jean‐Pierre, Chaloin, Laurent, Jordheim, Lars Petter, Peyrottes, Suzanne, Mathé, Christophe
• Format: Article
• Language: English
• Subjects: 5′-Ecto-nucleotidase; Adenosine; Biochemistry, Molecular Biology; Chemical Sciences; Cheminformatics; Enzymatic inhibitors; Immuno-oncology; Inhibitors; Life Sciences; Scaffolds; Structural Biology; Triazole derivatives; Triazoles
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202101175

The ecto‐5′‐nucleotidase CD73 is involved in the production of immunosuppressive adenosine in the tumoral microenvironment and recently became a validated target in immuno‐oncology. To avoid formation of CD73‐produced adenosine, several series of potential inhibitors of the target enzyme based on a triazole scaffold were synthetized and evaluated on recombinant purified hCD73 and in cell‐based assays. Several series of substituted 1,4,5‐triazole derivatives bearing various aryls, alkyls and indoles groups were synthetized, as inhibitors of 5′‐ectonucleotidase CD73, and evaluated for their potential inhibitory effect on purified recombinant hCD73 enzyme and in cell‐based assays. Among them, some compounds were found to be potent enzymatic inhibitors at 10 μM.