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• W2897976495 abstract "Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters." @default.
• W2897976495 created "2018-10-26" @default.
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• W2897976495 date "2018-12-01" @default.
• W2897976495 modified "2023-10-14" @default.
• W2897976495 title "Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors" @default.
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• W2897976495 doi "https://doi.org/10.1016/j.bmcl.2018.10.022" @default.
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