ChemInform Abstract: SYNTHESIS AND BIOLOGICAL ACTIVITY OF 3′‐AZIDO‐ AND 3′‐AMINO SUBSTITUTED NUCLEOSIDE ANALOGS

Abstract

Die Verbindungen (I) reagieren nach A) unter Bildung der Azide (III) und (IV) sowie der Anhydrouracile (V).

Design, Synthesis, and Biological Evaluation of Antiviral Agents Targeting Flavivirus Envelope Proteins

“…The only modification in structure 11 is that the R,βunsaturated ketone in M02 has been replaced by a bioisosteric amide, which was based on the same considerations with regard to toxicity as described above. To clarify the role of the 3,5diphenyl-1H-pyrazole moiety of M02 in its antiviral activity, 3,5-diphenyl-1H-pyrazole (17) itself was tested for antiviral activity.…”

“…Cryo-electron microscopy and X-ray crystallography studies of various flavivirus E protein fragments have revealed that domains I and II are connected by a mobile hinge that allows rotation of DII relative to DI-DIII during the processes of viral maturation and fusion of the viral envelope with the host cell membrane 14–17. Mutations that affect the pH threshold for either fusion or virulence are clustered in this hinge region 18–23.…”

“…Cryo-electron microscopy and X-ray crystallography studies of various flavivirus E protein fragments have revealed that domains I and II are connected by a mobile hinge that allows rotation of DII relative to DI−DIII during the processes of viral maturation and fusion of the viral envelope with the host cell membrane. – Mutations that affect the pH threshold for either fusion or virulence are clustered in this hinge region. – Furthermore, crystallization of a dengue virus type 2 E protein fragment in the presence of the detergent n -octyl-β- d -glucoside (β-OG) has led to structures with and without occupation of the hinge pocket by β-OG . Occupation of the pocket by β-OG requires an altered conformation of the kl loop toward an “open” position, and the angle that DII makes with DI−DIII also differs between two crystal structures with and without β-OG .…”