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Synfacts 2022; 18(01): 0006
DOI: 10.1055/s-0041-1737178
Synthesis of Natural Products and Potential Drugs

Synthesis of Dengue Virus Inhibitor JNJ-A07

Contributor(s):
Philip Kocienski
Van Loock M, *, Neyts J. * et al. Janssen Pharmaceutica, Beerse and KU Leuven, Belgium; Global Virus Network (GVN), Baltimore, USA
A Pan-serotype Dengue Virus Inhibitor Targeting the NS3–NS4B Interaction.

Nature 2021;
598: 504-509
DOI: 10.1038/s41586-021-03990-6.
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Key words

JNJ-A07 - antiviral - indolines

Significance

Dengue is a mosquito-borne disease that afflicts 96 million people annually, making it one of the top ten global health threats. There are no antiviral agents available to prevent or treat dengue. A dengue virus inhibitor (JNJ-A07) has been discovered that exerts nanomolar to pico­molar activity against a panel of 21 clinical isolates. JNJ-A07 blocks the interaction between two viral proteins (NS3 and NS4B), thus revealing a previously undescribed mechanism of antiviral action.


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Comment

The synthesis of JNJ-A07 depicted is taken from an associated patent (WO 2017 167951 A1, Example 4B). This simple and conventional approach delivered 24 substituted indoline analogues which included the enantiomers arising from the single stereogenic center. These were separated by chiral supercritical fluid chromatography. The dextrorotatory enantiomer of unknown absolute configuration corresponds to JNJ-A07.


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Publication History

Article published online:
17 December 2021

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