Tetrazoles are doubly unsaturated five-membered aromatic heterocycles consisting of one carbon atom and four nitrogen atoms. Tetrazole derivatives are a major class of heterocyclic compounds that are important for medicinal chemistry and drug design because of their not only isosteric properties with carboxylic acid and amide moieties, but also metabolic stability and other beneficial physicochemical properties.
ORIC-533 is a potential best-in-class, oral inhibitor of CD73 developed by ORIC Pharmaceuticals which is currently in a Ph. Ib trial for the treatment of relapsed/refractory multiple myeloma (MM). It inhibits the CD73-mediated conversion of AMP to adenosine which generates an immunosuppressive tumor microenvironment and has the potential to be a next-generation immunotherapy. The in-depth use of co-crystal structures led the team to discover a novel set of phosphonate bioisosteres which were able to achieve bioavailability for a highly polar scaffold. The structure and discovery story of ORIC-533 were recently presented at the ACS Spring 2024 Meeting in New Orleans. Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.
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