Synthesis and structure-activity relationship of RXR antagonists based on the diazepinylbenzoic acid structure

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 17, 2007, Pages 4808-4811

  Sakaki, Junichi ^a   Konishi, Kazuhide ^a   Kishida, Masashi ^a   Gunji, Hiroki ^a   Kanazawa, Takanori ^a   Uchiyama, Hidefumi ^a   Fukaya, Hiroaki ^a   Mitani, Hironobu ^a   Kimura, Masaaki ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Antagonist; Diazepinylbenzoic acid; RXR

Indexed keywords

4 [2,3 (2,5 DIMETHYL 2,5 HEXANO) 5 METHYL 5H DIBENZO[B,E][1,4]DIAZEPIN 11 YL]BENZOIC ACID; 6 [1 (5,6,7,8 TETRAHYDRO 3,5,5,8,8 PENTAMETHYL 2 NAPHTHYL)CYCLOPROPYL]NICOTINIC ACID; AMINE; BENZOIC ACID DERIVATIVE; CELL NUCLEUS RECEPTOR; DIAZEPINYLBENZOIC ACID; FARNESOID X RECEPTOR; HX 531; LIVER X RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; RECEPTOR BLOCKING AGENT; RETINOIC ACID RECEPTOR; RETINOID X RECEPTOR; SULFONAMIDE; TAMIBAROTENE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG EFFECT; DRUG STRUCTURE; DRUG SYNTHESIS; ENERGY EXPENDITURE; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN SENSITIVITY; LIPID DIET; NONHUMAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; WEIGHT GAIN;

ADMINISTRATION, ORAL; BENZOIC ACIDS; BIPHENYL COMPOUNDS; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; MOLECULAR STRUCTURE; RECEPTORS, RETINOIC ACID; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS; TRANS-ACTIVATION (GENETICS); TRANS-ACTIVATORS; TRANSCRIPTION FACTORS;

EID: 34547542759     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.06.079     Document Type: Article

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8. 3) δ: 1.06 (3H, s), 1.14 (3H, s), 1.21 (3H, t), 1.26 (3H, s), 1.31 (3H, s), 1.62-1.70 (4H, m), 3.53-3.72 (2H, m), 6.42 (1H, s), 6.84-6.88 (3H, m), 6.92-6.96 (2H, m), 7.59 (1H, t), 7.78 (1H, d), 7.86 (2H, d), 7.95-7.97 (3H, m), 8.13 (1H, d).
9. 6) δ: 0.80 (3H, t), 1.01 (3H, s), 1.10 (3H, s), 1.23 (3H, t), 1.27 (3H, s), 1.44-1.62 (6H, m), 3.37-3.43 (1H, m), 3.65-3.70 (1H, m), 6.84-6.99 (5H, m), 7.73 (2H, d), 7.82 (1H, t), 7.90 (1H, s), 7.99-8.07 (4H, m), 10.29 (1H, br s), 13.14 (1H, br s).
10. 6 cells/mL) was mixed with DNA-LipofectAmine2000 (50 μL/well in OPTI-MEM I serum free medium) and dispensed to the wells of a 96-well flat-bottomed assay plate. After a 6-h incubation, 2 nM LG100268 or 20 nM 9-cis-RA as the activating ligands was added in the presence or absence of a test compound ατ 0.001 τo 10 μM (final concentration) as dilutions of 50 μL/well of the medium. After further 20 h incubation, the cells were lysed and the luciferase activity was measured.