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The most potent compounds were those characterized by a substitution in the para-position of the C-ring.
Activities of most potent compounds were also compared with a commercial organophosphorus compound.
Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity.
Of the most potent compounds, 9e displayed an IC50 value for BACE1 of 98 nM.
Compounds 9 and 13 were the most potent compounds in tumor necrosis without liver necrosis.
The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5 nM.
The most potent compounds were selective towards tankyrases over a panel of other human ARTD enzymes.
Furthermore, the most potent compounds showed low cytotoxic effects against HFF-1 normal cell line.
The open chain analogs 36 and 42 were shown to be the most potent compounds.
Most potent compounds showed good potency in both enzymatic and functional human whole blood assay.
Five most potent compounds with nanomolar IC50 values were selected for pharmacokinetics and in vivo experiments.
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