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• W1988337941 startingPage "2587" @default.
• W1988337941 abstract "A series of substituted-isoxazole derivatives was prepared as candidate farnesoid X receptor (FXR) antagonists, based on our previously proposed ligand superfamily concept. Structure–activity relationship studies indicated that the shape and the structural bulkiness of the substituent at the 5-position of the isoxazole ring affected FXR-antagonistic activity. Compounds 15g (5-substituent: 2-naphthyl) and 15h (5-substituent: 4-biphenyl) were identified as potent antagonists with higher selectivity for FXR over progesterone receptor than the naturally occurring FXR antagonist GS. The 5-substituent is also a critical determinant of the characteristic corepressor recruitment profile of this class of FXR antagonists, though distinct mechanisms appear to be involved: 15h stabilizes the corepressor-nuclear receptor interaction, while 15g inhibits coactivator recruitment." @default.
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• W1988337941 date "2007-04-01" @default.
• W1988337941 modified "2023-10-03" @default.
• W1988337941 title "Design, synthesis, and evaluation of non-steroidal farnesoid X receptor (FXR) antagonist" @default.
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• W1988337941 doi "https://doi.org/10.1016/j.bmc.2007.01.046" @default.
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