Enantiomeric 4′-Truncated 3-deaza-1′, 6′-isoneplanocins: Synthesis and antiviral properties including Ebola. Issue 17 (1st September 2019)

• Record Type: Journal Article
• Authors: Liu, Chong; Coleman, Rachel; Archer, Ashley; Hussein, Islam; Bowlin, Terry L.; Chen, Qi; Schneller, Stewart W.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 17(2019)
• Page Start: 2480
• Page End: 2482
• Publication Date: 2019-09-01
• Subjects: Carbocyclic nucleosides -- 3-Deazaisoneplanocin -- Ebola -- HCMV -- Measles -- Norovirus -- Pichinde virus; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.07.021
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Enantiomeric 3-deaza-1′, 6′-isoneplanocins (C-3 unsubstituted7a /7b and C-3 with a bromine8a /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-like7a and8a andL -like8b . All four products showed effects against human cytomegalovirus while D-like7a /8a affected measles;7a was effective versus norovirus and8a inhibited Pichinde. Both7a and8a produced SAHase inhibitory effects. However, the anti-EBOV activity of7a and8a cannot be readily correlated with this observation due with their contrasting IC50 values (8a > 7a ). It is to be noted that7b showed no effects on this enzyme and8b 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.