X. Yao, Xiuyun Sun, Shuyu Jin
Jul 1, 2019
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0
Influential Citations
20
Citations
Quality indicators
Journal
Journal of medicinal chemistry
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 analogs 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.