- Micromolecular reversible BTK inhibitor for treating rheumatoid arthritis
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The invention relates to a micromolecular reversible BTK inhibitor for treating rheumatoid arthritis, and specifically provides a compound. The compound is the compound as shown in a formula I, or a stereisomer, a geometrical isomer and a tautomer thereof, nitric oxide, aquo-complex, a solvate, a metabolite and pharmaceutically acceptable salts and prodrugs. The inventor finds that polysubstitutedquinolone compound or derivate thereof as shown in formula I can be used as the BTK inhibitor and is high in activity during treating rheumatoid arthritis.
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Paragraph 0140-0141; 0145-0148
(2019/07/29)
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- Discovery of 4-Aminoquinoline-3-carboxamide derivatives as potent reversible Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis
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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.
- Yao, Xia,Sun, Xiuyun,Jin, Shuyu,Yang, Ling,Xu, Hongjiang,Rao, Yu
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p. 6561 - 6574
(2019/08/20)
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