Fragmentation of GW4064 led to a highly potent partial farnesoid X receptor agonist with improved drug-like properties

Bioorganic and Medicinal Chemistry

Volumn 23, Issue 13, 2015, Pages 3490-3498

  Flesch, Daniel ^a   Gabler, Matthias ^a   Lill, Andreas ^a   Gomez, Roberto Carrasco ^a   Steri, Ramona ^a   Schneider, Gisbert ^b   Stark, Holger ^c   Schubert Zsilavecz, Manfred ^a   Merk, Daniel ^a  

^a GOETHE UNIVERSITY   (Germany)

^b ETH ZURICH   (Switzerland)

^c HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

Farnesoid X receptor; Fluorescent FXR ligand; FXR agonists; Metabolic disorders; Nuclear receptors

Indexed keywords

3 (3 O TOLYL 1,2,4 OXADIAZOL 5 YL)BENZOIC ACID; 3 [2 [2 CHLORO 4 [3 (2,6 DICHLOROPHENYL) 5 ISOPROPYL 4 ISOXAZOLYLMETHOXY]PHENYL]VINYL]BENZOIC ACID; 3,5 DIPHENYL 1,2,4 OXADIAZOLE; 4 (3 O TOLYL 1,2,4 OXADIAZOL 5 YL)BENZOIC ACID; 4 (3 PHENYL 1,2,4 OXADIAZOL 5 YL)PHENOL; 5 (4 BROMOPHENYL) 3 PHENYL 1,2,4 OXADIAZOLE; 5 (4 CHLOROPHENYL) 3 P TOLYL 1,2,4 OXADIAZOLE; 5 (4 METHOXYPHENYL) 2 P TOLYL 1,3 THIAZOL 4 OL; 5 (4 METHOXYPHENYL) 3 O TOLYL 1,2,4 OXADIAZOLE; 5 (4 METHOXYPHENYL) 3 PHENYL 1,2,4 OXADIAZOLE; 5 (4 METHOXYPHENYL) 3 [3 (TRIFLUOROMETHYL)PHENYL] 1,2,4 OXADIAZOLE; 5 ISOPROPYL 3 PHENYL 1,2,4 OXADIAZOLE; 7 (DIETHYLAMINO) 2 OXO 2H CHROMENE 3 CARBOXYLIC ACID; 7 (DIETHYLAMINO) 3 (3 PHENYL 1,2,4 OXADIAZOL 5 YL) 2H CHROMEN 2 ONE; FARNESOID X RECEPTOR; N HYDROXY 2 METHYLBENZAMIDINE; N HYDROXY 3 (TRIFLUOROMETHYL)BENZAMIDINE; N HYDROXY 4 METHYLBENZAMIDINE; N HYDROXYBENZAMIDINE; UNCLASSIFIED DRUG; CELL RECEPTOR; FARNESOID X-ACTIVATED RECEPTOR; ISOXAZOLE DERIVATIVE; LIGAND;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG METABOLISM; DRUG POTENCY; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; EC50; FRAGMENTATION REACTION; HELA CELL LINE; IN VITRO STUDY; LIVER MICROSOME; MOLECULAR DOCKING; MOLECULAR WEIGHT; NONHUMAN; PROCESS OPTIMIZATION; PROTEIN BINDING; PROTEIN DOMAIN; RAT; STRUCTURE ACTIVITY RELATION; AGONISTS; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; GENE EXPRESSION; GENETIC TRANSFECTION; GENETICS; HEPG2 CELL LINE; HUMAN; HYDROLYSIS; METABOLISM; PLASMID; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; X RAY CRYSTALLOGRAPHY;

CELL SURVIVAL; CRYSTALLOGRAPHY, X-RAY; GENE EXPRESSION; HELA CELLS; HEP G2 CELLS; HUMANS; HYDROLYSIS; ISOXAZOLES; LIGANDS; MOLECULAR DOCKING SIMULATION; PLASMIDS; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, CYTOPLASMIC AND NUCLEAR; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION;

EID: 84937423303     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2015.04.035     Document Type: Article

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