Cyclohexyl-linked tricyclic isoxazoles are potent and selective modulators of the multidrug resistance protein (MRP1)

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 24, 2005, Pages 5526-5530

  Norman, Bryan H ^a   Lander, Peter A ^a   Gruber, Joseph M ^a   Kroin, Julian S ^a   Cohen, Jeffrey D ^a   Jungheim, Louis N ^a   Starling, James J ^a   Law, Kevin L ^a   Self, Tracy D ^a   Tabas, Linda B ^a   Williams, Daniel C ^a   Paul, Donald C ^a   Dantzig, Anne H ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Isoxazole; MRP; Multidrug resistance; Tricyclic

Indexed keywords

DOXORUBICIN; GLYCOPROTEIN P; ISOXAZOLE DERIVATIVE; MULTIDRUG RESISTANCE PROTEIN 1; VINCRISTINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL LINE; CELL STRAIN HL 60; CONTROLLED STUDY; CYTOTOXICITY; DRUG POTENCY; DRUG SELECTIVITY; HELA CELL; HUMAN; HUMAN CELL; MEMBRANE VESICLE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; STRUCTURE ACTIVITY RELATION; TUMOR REGRESSION;

ANTINEOPLASTIC AGENTS; HELA CELLS; HUMANS; ISOXAZOLES; KINETICS; MOLECULAR CONFORMATION; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 27644591577     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.08.075     Document Type: Article

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12. The relative stereochemistry of the syn and anti bis-substituted cyclohexyl derivatives (14, 15, and 19-21) was determined using spectroscopic methods and will be described in a forthcoming publication.
13. Assay conditions have been previously described. See Ref. 3 (and references cited therein).
14. An enantiospecific synthesis has been developed and the absolute stereochemistries have been determined for compounds in the cyclohexyl-linked series. This work will be described in a forthcoming publication.
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