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ID: ALA4229503

Journal: Bioorg Med Chem

Title: Discovery of novel Syk/PDGFR-α/c-Kit inhibitors as multi-targeting drugs to treat rheumatoid arthritis.

Authors: Li X, Huang Y, Cheng J, Zhang L, Mao F, Zhu J, Sheng C, Li J.

Abstract: Due to the complex biological pathways involved in rheumatoid arthritis, discovery of multi-targeting small molecules provides an effective strategy to achieve better efficacy and lower toxicity. Herein the first Syk/PDGFR-α/c-Kit inhibitors were designed and evaluated. Dihydrofuropyrimidine derivative 13 showed potent inhibitory activity against the three targets. Importantly, compound 13 exhibited good cellular efficacy against fibroblast-like synoviocytes (IC50 = 3.21 μM) and mouse bone marrow-derived mast cells (IC50 = 2.03 μM) and significantly decreased the secretion of inflammatory cytokines. Thus, Syk/PDGFR-α/c-Kit triple inhibitor 13 represented a promising lead compound for the treatment of RA.

CiteXplore: 30078608

DOI: 10.1016/j.bmc.2018.06.029