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Adenosine analogue nucleosides are a fundamental part of medicinal chemistry. Tubercidin is a well-known example, but its application is limited due to high toxicity. The development of less toxic synthetic analogues is therefore highly desirable. Here we show the synthesis of fluorinated nucleosides based on the pyrrolo[2,3- d]pyrimidine (7-deazapurine) motif. The synthetic approach is based on an easily accessible trifluoromethylated acetoacetate and several amidines, as building blocks. This allows for simultaneous introduction of a CF3 group as well as a variety of C2 substituents for the synthesis of the heterocyclic part, including alkyl, aryl, SMe, Cl, N3 and NH2 moieties. Glycosylation of the fully pre-functionalized heterocycles proceeds with excellent β-selectivity. Cytotoxicities were determined using an AlamarBlue assay with HeLa S3 and Hep G2 cancer cell lines. The effect of C2 substitution was explored and a lead structure candidate with IC50 values of 90 ± 49 nM (HeLa S3) and 28 ± 9 nM (Hep G2) was identified. [ABSTRACT FROM AUTHOR]

With the purpose to synthesize novel ADAs (adenosine deaminase) and IMPDH (inosine 5′-monophosphate dehydroge�nase) inhibitors the reaction of 5-amino-1-tert-butyl-1H-pyrrolo-3-carbonitrile with fluorinated 1,3-biselectrophiles was studied. An efficient and convenient synthetical approach to obtain fluorinated pyrrolo[2,3-b]pyridines was developed. tert-Butyl protecting group was successfully cleaved by treating of synthesized pyrrolo�pyridines with concentrated sulfuric acid. [ABSTRACT FROM AUTHOR]

This communication describes a practical and facile one-pot approach for the synthesis of 7-trifluoromethyl-substituted imidazo[4,5-b]pyridines by the reaction of in situ generated 5-aminoimidazole and a 1,3-CCC-biselectrophile. [ABSTRACT FROM AUTHOR]