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ID: ALA4814022

Journal: Bioorg Med Chem Lett

Title: Enantiomeric 4'-truncated 6'-fluoro-3-deazaneplanocin and its 3-bromo derivative: Synthesis and antiviral properties, including Ebola and Marburg.

Authors: Haverkamp C, Liu C, Schneller SW.

Abstract: In seeking to increase the library of fluorine containing adenine-derived carbocyclic nucleoside antiviral candidates, d-like and l-like 6'-fluoro-3-deazaneplanocin and its 3-bromo derivative lacking the 4'-hydroxylmethylene substituent (2/3 and 4/5, respectively) are presented. Their synthesis was accomplished from d-ribose by developing a more facile precursor route than suggested by the literature. The 2/4d-like pair displayed significant anti-filo virial properties while the enantiomeric l-like congeners 3/5 were inactive. Target compounds 2/4 also were active towards measles and norovirus. The effect of 2/4 is further evidence of the role fluoro-derived adenine carbocyclic nucleoside can play in antiviral drug discovery. Furthermore, the simplicity of their synthesis lends them to more efficacious analogs and to scale-up optimization. There were no other relevant antiviral properties for 2/3 and 4/5 (except BK polyomavirus for 3/5).

CiteXplore: 33766766

DOI: 10.1016/j.bmcl.2021.127985