1. Practical and Divergent Synthesis of Carbocyclic Pyrazolo[3,4‐d]pyrimidine Nucleoside Analogues.
- Author
-
Van de Velde, Ewout, Van Hauwermeiren, Anouk, Van Pelt, Natascha, Matheeussen, An, Caljon, Guy, and Van Calenbergh, Serge
- Subjects
- *
PYRIMIDINES , *TRYPANOSOMA brucei , *NUCLEOSIDE derivatives , *HYDRAZINE , *NUCLEOPHILES , *URIDINE , *SUBSPECIES , *HYDRAZINES - Abstract
A concise set of 4‐substituted pyrazolo[3,4‐d]pyrimidine carboriboside analogues was synthesized in a divergent fashion via a central intermediate. An oxaziridine reagent allowed the synthesis of a crucial hydrazine glycon intermediate, which was transformed through a base‐build‐up strategy into the desired intermediate using a commercially available pyrimidine building block. Reaction with a variety of nucleophiles allowed late‐stage diversification. All analogues were evaluated for activity against a representative panel of Trypanosomatida. A methoxy‐substituted analogue displayed single‐digit micromolar activity against two subspecies of Trypanosoma brucei in cellular assays. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF