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

Bioorg Med Chem Lett. 2023 Mar 8:129219. doi: 10.1016/j.bmcl.2023.129219. Online ahead of print.ABSTRACTTo 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.PMID:36898483 | DOI:10.1016/j.bmcl.2023.129219

Source: Bioorganic and Medicinal Chemistry Letters - March 10, 2023 Category: Chemistry Authors: Chong Liu Qi Chen Stewart W Schneller Source Type: research