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ID: ALA4334462

Journal: Bioorg Med Chem Lett

Title: Enantiomeric 4'-Truncated 3-deaza-1',6'-isoneplanocins: Synthesis and antiviral properties including Ebola.

Authors: Liu C, Coleman R, Archer A, Hussein I, Bowlin TL, Chen Q, Schneller SW.

Abstract: Enantiomeric 3-deaza-1',6'-isoneplanocins (C-3 unsubstituted 7a/7b and C-3 with a bromine 8a/8b) lacking the 4'-hydroxymethyl as mechanistically designed anti-viral targets have been prepared by utilizing the Ullmann reaction. Anti-Ebola properties were found for the D-like 7a and 8a and L-like 8b. All four products showed effects against human cytomegalovirus while D-like 7a/8a affected measles; 7a was effective versus norovirus and 8a inhibited Pichinde. Both 7a and 8a produced SAHase inhibitory effects. However, the anti-EBOV activity of 7a and 8a cannot be readily correlated with this observation due with their contrasting IC50 values (8a > 7a). It is to be noted that 7b showed no effects on this enzyme and 8b was minimally inhibitory. These results offer preliminary insight into the differing mechanisms of action of D- and L- like structures and enlighten structural features to guide additional antiviral agent pursuit in the isoneplanocin series.

CiteXplore: 31358469

DOI: 10.1016/j.bmcl.2019.07.021