FIELD: chemistry.
SUBSTANCE: invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof, which can be used as farnesoid-X receptor agonists. In formula IY is carbon; each of R1 and R2 independently represents hydrogen, halogen or trifluoromethyl; Z is n equals 0, 1 or 2; each of X1, X2 and X3 independently represents carbon or nitrogen; each of R3 and R4 independently represents hydrogen, halogen, cyano, C1-6alkyl, C3-6cycloalkyl, halo-C1-6 alkyl, CONRa1Ra2, NRa1Ra2, CH2NRa1Ra2, CH2Rc3, CORa3, ORa3, NRa4CORa3, NRa4CO2Ra3, NHCONHRa3 or 3- or 8-member heterocycles, which in their structure contain one or two oxygen or nitrogen atoms, where m equals 1 or 2; each of Ra1 and Ra2 independently represents hydrogen, C1-6alkyl, C3-6cycloalkyl, halo-C1-6alkyl or 3- or 8-member heterocycles, which in their structure contain one or two oxygen atoms or nitrogen; Ra3 is hydrogen, C1-6alkyl, C3-6cycloalkyl, halo-C1-6alkyl, or 3- or 8-member heterocycles, which in their structure contain one or two oxygen or nitrogen atoms; Ra4 is hydrogen or C1-6alkyl; R5 is hydrogen, each of R6 and R7 independently represents hydrogen, halogen, trifluoromethyl or trifluoromethoxy; Rc3 represents hydrogen or C1-6alkyl; each of W1, W2 and W3 independently represents oxygen, nitrogen, CRw1 or NRw1, where Rw1 is hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkylamine, C1-6alkyl alcohol, or (CH2)pheteroaryl, where heteroaryl is 6-member monocyclic ring with one nitrogen atom, and p is equal to 1, 2 or 3. Invention also relates to a pharmaceutical composition for affecting a farnesoid-X receptor containing said compound of formula I or a pharmaceutically acceptable salt thereof.
EFFECT: disclosed are isoxazole derivatives as nuclear receptor agonists and use thereof.
7 cl, 2 tbl, 115 ex
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Authors
Dates
2021-01-25—Published
2018-04-12—Filed