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

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.