2-Alkyl-4-arylimidazoles: Structurally novel sodium channel modulators

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 13, 2004, Pages 3521-3523

  Liberatore, Anne Marie ^a   Schulz, Jocelyne ^a   Pommier, Jacques ^a   Barthelemy, Marie Anne ^a   Huchet, Marion ^a   Chabrier, Pierre Etienne ^a   Bigg, Dennis ^a  

^a Institut Henri Beaufour   (France)

Author keywords

[No Author keywords available]

Indexed keywords

IMIDAZOLE DERIVATIVE; SODIUM CHANNEL BLOCKING AGENT;

ARTICLE; BINDING AFFINITY; BINDING SITE; DRUG POTENCY; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZIMIDAZOLES; BINDING SITES; BRAIN; CARBOLINES; CELLS, CULTURED; ELECTROPHYSIOLOGY; INHIBITORY CONCENTRATION 50; RATS; SODIUM CHANNEL BLOCKERS; SODIUM CHANNELS; STRUCTURE-ACTIVITY RELATIONSHIP; VERATRIDINE;

EID: 2942618884     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.04.059     Document Type: Article

References (8)

1. Clare J.J., Tate S.N., Nobbs M., Romanos M.A. Drug Discovery Today. 5:2000;506-520
2. Thurieau, C. A.; Poitout, L. F.; Galcera, M.-O.; Moinet, C. P.; Gordon, T. D.; Morgan, B. A.; Bigg, D. C.; Pommier J. WO 9964420, Chem. Abstr. 1999, 132, 35702
3. Gordon T.D., Singh J., Hansen P.E., Morgan B.A. Tetrahedron Lett. 34:1993;1901
4. Frechet J.M.J., Farall M.J. J. Macromol. Sci., Chem. 1997;507
5. Rather J.B., Rfid E. Emmet J. Am. Chem. Soc. 41:1919;75-83
6. 4, 5.5 mM glucose, 130 mM choline chloride (pH 7.4) to give a final concentration of about 4 mg protein/mL and stored at -80°C until use. Protein concentration was determined by the Bradford method using bovine serum albumine as a standard.
7. 50 value was the concentration, which decreased the % of cell injury by 50% and was derived by extrapolation from graphs of dose-response relations. Values used for calculations are the mean values of triplicates
8. Selected data for compound 2g: Typical experimental procedure. Synthesis of 2g: 4-(1, 1′-biphenyl-4-yl)-2-(1-pentylhexyl)-1H-imidazole (2g). Caesium carbonate (2.03 g, 6.25 mmol) was added to a solution of dipentylacetic acid (2.5 g, 12.5 mmol) in methanol (50 mL). The reaction mixture was stirred for 1 h, the solvent was evaporated, and 4′-phenyl bromoacetophenone (3.43 g, 12.5 mmol) and dimethylformamide (40 mL) were added and the mixture stirred overnight. The reaction mixture was evaporated to dryness under reduced pressure and xylene (60 mL) added to the residue. The caesium bromide salt was filtered, ammonium acetate (20 g) added to the filtrate and the reaction mixture refluxed for 1.5 h using a Dean-Stark apparatus. After cooling, the reaction was diluted with ice water and ethyl acetate (200 mL). The organic phase was washed with a saturated solution of sodium bicarbonate (2 × 100 mL) followed by brine (100 mL), dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. Purification was carried out on a silica gel column (mobile phase: 5% methanol in dichloromethane) The evaporated fractions were suspended in diethyl ether (50 mL), filtered and rinsed with the same volume of ether to afford 0.46 g (10%) of 2g as a light cream powder.