Various N-fused isoquinoline derivatives were synthesized using a new one-pot reaction of 1-bromo-2-(2,2-difluorovinyl)benzenes with N-H group containing heterocycles followed by intramolecular palladium-catalyzed C-H arylation. The method described gives convenient access to diverse structures of N-fused polycyclic isoquinolines. Sixteen of the synthesized compounds were screened as potential human nucleotide pyrophosphatase/phosphodiesterase 1 and 3 (h-NPP-1 and h-NPP-3) inhibitors. The most effective h-NPP-1 inhibitor showed an IC value as high as 0.36 ± 0.06 μM, whereas the most potent h-NPP-3 inhibitor posessed an inhibitory value of 0.48 ± 0.01 μM. Kinetic and molecular docking studies of both most effective inhibitors were carried out.
We
report base-mediated reactions of 1-bromo-2-(2,2-difluorovinyl)benzenes
with phenols followed by Pd-catalyzed intramolecular C–H arylation,
which offers a novel route to a pharmaceutically relevant class of
compounds, oxepines. Construction of these medium-sized ring structures
proceeds as a one-pot two-step reaction through diaryl ketene acetals
as intermediates. It allows to obtain various dibenz[b,d]oxepine derivatives in moderate to high yields.
A series of thienoindolizine structural isomers have been synthesized in a one-pot, two-step procedure starting from easily accessible gem-difluoroalkene functionalized bromothiophenes. The developed method gives easy access to a range of thienoindolizine products containing thieno[3,2g]-, thieno[3,4-g]-and thieno[2,3-g]indolizine core structures. The described synthesis strategy consists of a base mediated, transition metal free nucleophilic substitution of fluorine atoms by nitrogen containing heterocycles followed by a Pd catalyzed intramolecular cyclization. A series of 22 final product examples has been obtained with yields ranging from 29 % to 95 %. UV/Vis absorption, fluorescence spectroscopy, fluorescence lifetime measurements and cyclic voltammetry were carried out with selected final products to evaluate structural effects on photophysical and electrochemical properties. (TD)DFT and NICS calculations were performed to provide insight into the electronic properties of the four core molecular structures.
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