2- and 3-Fluoro-3-deaza-1',6'-isoneplanocin: Synthesis and antiviral properties (including Ebola and Marburg)

Chong Liu; Qi Chen; Stewart W Schneller

doi:10.1016/j.bmcl.2023.129219

2- and 3-Fluoro-3-deaza-1',6'-isoneplanocin: Synthesis and antiviral properties (including Ebola and Marburg)

Bioorg Med Chem Lett. 2023 Apr 1:85:129219. doi: 10.1016/j.bmcl.2023.129219. Epub 2023 Mar 8.

Authors

Chong Liu¹, Qi Chen², Stewart W Schneller³

Affiliations

¹ Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, USA.
² Department of Chemistry, Slippery Rock University, Slippery Rock, PA 16057, USA.
³ Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, USA. Electronic address: schnest@auburn.edu.

PMID: 36898483
DOI: 10.1016/j.bmcl.2023.129219

Abstract

To extend the antiviral properties of 2- and 3-fluoro-3-deazaneplanocins into the evolving 3-deaza-1',6'-isoneplanocin library, 2- (11) and 3-fluoro-1',6'-iso-3-deazaneplanocin A (12) have been explored. The requisite synthesis began with an Ullmann reaction by coupling of a protected cyclopentenyl iodide with either 2-fluoro- or 3-fluoro-3-deazaadenine. Target 12 displayed significant activity towards 5 viruses (μM): H1N1 (EC₅₀ < 0.36, CC₅₀ > 357, SI > 1000), hepatitis B virus (EC₅₀ 1.28, CC₅₀ > 357, SI > 279), norovirus (EC₅₀ 0.64, CC₅₀ > 357, SI > 558), Ebola (EC₅₀ < 0.1, CC₅₀ > 100, SI > 1000), and Marburg (EC₅₀ < 0.1, CC₅₀ > 100, SI > 1000). On the other hand, while 11 showed limited antiviral effects, its toxicity was significant, precluding any further usefulness.

Keywords: 3-deaza-1′,6′-isoneplanocin; Carbocyclic nucleosides; Ebola; H1N1; Hepatitis B virus; Marburg; Norovirus; Ullmann coupling.

MeSH terms

Adenosine
Antiviral Agents / pharmacology
Ebolavirus*
Hemorrhagic Fever, Ebola* / drug therapy
Humans
Influenza A Virus, H1N1 Subtype*

Substances

Adenosine
Antiviral Agents