3 research outputs found
Palladium(II)-Catalyzed Synthesis of 2<i>H</i>,3ā²<i>H</i>āSpiro[benzofuran-3,2ā²-naphthoquinones]
2<i>H</i>,3ā²<i>H</i>-SpiroĀ[benzofuran-3,2ā²-naphthoquinones],
constituting a new spiroheterocyclic skeleton, were synthesized starting
from 2-aryloxymethyl-1,4-naphthoquinones by means of a palladiumĀ(II)-catalyzed
reaction, which is a new spirocyclic transformation. Under optimal
conditions, i.e. 10 mol % of palladiumĀ(II) acetate, 15 mol % of 3,5-dichloropyridine,
and 5 mol % of trifluoroacetic acid in acetic acid at 110 Ā°C,
various 2<i>H</i>,3ā²<i>H</i>-spiroĀ[benzofuran-3,2ā²-naphthoquinones]
were synthesized in yields strongly dependent on the substitution
pattern of the aryloxy group. Unsubstituted or <i>ortho</i>-substituted 2-aryloxymethyl-1,4-quinones were found to rearrange
toward the corresponding 2-(4-hydroxyaryl)-1,4-quinones upon treatment
with trifluoroacetic acid
Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor
Dengue
is a global public health threat, with about half of the
worldās population at risk of contracting this mosquito-borne
viral disease. Climate change, urbanization, and global travel accelerate
the spread of dengue virus (DENV) to new areas, including southern
parts of Europe and the US. Currently, no dengue-specific small-molecule
antiviral for prophylaxis or treatment is available. Here, we report
the discovery of JNJ-1802 as a potent, pan-serotype DENV
inhibitor (EC50ās ranging from 0.057 to 11 nM against
the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in
human hepatocytes, the absence of major in vitro pharmacology safety
alerts, and a dose-proportional increase in efficacy against DENV-2
infection in mice were all supportive of its selection as a development
candidate against dengue. JNJ-1802 is being progressed
in clinical studies for the prevention or treatment of dengue
Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor
Dengue
is a global public health threat, with about half of the
worldās population at risk of contracting this mosquito-borne
viral disease. Climate change, urbanization, and global travel accelerate
the spread of dengue virus (DENV) to new areas, including southern
parts of Europe and the US. Currently, no dengue-specific small-molecule
antiviral for prophylaxis or treatment is available. Here, we report
the discovery of JNJ-1802 as a potent, pan-serotype DENV
inhibitor (EC50ās ranging from 0.057 to 11 nM against
the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in
human hepatocytes, the absence of major in vitro pharmacology safety
alerts, and a dose-proportional increase in efficacy against DENV-2
infection in mice were all supportive of its selection as a development
candidate against dengue. JNJ-1802 is being progressed
in clinical studies for the prevention or treatment of dengue