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• W2617863789 abstract "Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted optimization studies of our lead compound 1, which we previously reported as a novel VAP-1 inhibitor, to enhance the inhibition of human VAP-1 and to reduce CYP3A4 and CYP2C19 inhibition. As a result, we identified 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino]methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid (17h) as a novel orally active VAP-1 inhibitor, with 14-fold increased human VAP-1 inhibitory activity compared to 1, without CYP3A4 and CYP2C19 inhibition. Oral administration of 17h significantly inhibited the progression of proteinuria in streptozotocin (STZ) induced diabetic rats at 0.3 and 1 mg/kg, suggesting that this compound has potential to be a therapeutic agent for the treatment of diabetic nephropathy." @default.
• W2617863789 created "2017-06-05" @default.
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• W2617863789 date "2017-08-01" @default.
• W2617863789 modified "2023-09-27" @default.
• W2617863789 title "Synthesis and pharmacological evaluation of glycine amide derivatives as novel vascular adhesion protein-1 inhibitors without CYP3A4 and CYP2C19 inhibition" @default.
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• W2617863789 doi "https://doi.org/10.1016/j.bmc.2017.05.059" @default.
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