Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 4, 2011, Pages 1134-1140

  Richter, Hans G F ^a   Benson, G M ^a   Bleicher, K H ^a   Blum, D ^a   Chaput, E ^a   Clemann, N ^a   Feng, S ^b   Gardes, C ^a   Grether, U ^a   Hartman, P ^a   Kuhn, B ^a   Martin, R E ^a   Plancher, J M ^a   Rudolph, M G ^a   Schuler, F ^a   Taylor, S ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b Roche RandD Center China Ltd   (China)

Author keywords

ADME; Farnesoid X receptor agonist; FXR; Lead optimization; Nuclear receptor; X ray structure

Indexed keywords

4 [2 [2 (4 CHLORO PHENYL) 5,6 DIFLUORO BENZOIMIDAZOL 1 YL] 2 CYCLOHEXYL ACETYLAMINO] 3 FLUORO BENZOIC ACID; ANTILIPEMIC AGENT; BENZIMIDAZOLE DERIVATIVE; FARNESOID X RECEPTOR AGONIST; HORMONE RECEPTOR STIMULATING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; DRUG CLEARANCE; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; IC 50; MALE; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; RAT; STRUCTURE ACTIVITY RELATION;

4-AMINOBENZOIC ACID; ADMINISTRATION, ORAL; ANIMALS; BENZIMIDAZOLES; BINDING SITES; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; HUMANS; MALE; MICE; MICE, INBRED C57BL; MICROSOMES, LIVER; MOLECULAR CONFORMATION; RATS; RATS, WISTAR; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, LDL; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS;

EID: 79851510529     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.12.123     Document Type: Article

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