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- W2954400172 abstract "A structure-hopping strategy was applied to discover a series of novel 4-aminoquinoline-3-carboxamide derivatives as potent, reversible BTK inhibitors. Compared to the previously described cinnoline scaffold compounds, the 4-aminoquinoline analogues showed significantly improved drug-like properties, especially in their aqueous solubility. The most potent compound, 25, displayed a stronger inhibitory effect on both BTKWT (IC50 = 5.3 nM) and BTKC481S (IC50 = 39 nM). In a rodent collagen-induced arthritis model, compound 25 efficiently reduced paw swelling without a loss in body weight. On the basis of potency, drug-like properties, stability, and noncovalent mode of inhibition, our representative inhibitors could have a promising profile to be treatments for a wide range of autoimmune diseases." @default.
- W2954400172 created "2019-07-12" @default.
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- W2954400172 date "2019-07-01" @default.
- W2954400172 modified "2023-10-15" @default.
- W2954400172 title "Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis" @default.
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- W2954400172 doi "https://doi.org/10.1021/acs.jmedchem.9b00329" @default.
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