2,4(5)-Diarylimidazoles: Synthesis and biological evaluation of a new class of sodium channel blockers against hNav1.2

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 20, 2008, Pages 5460-5462

  Rivara, Mirko ^a   Baheti, Aparna R ^b   Fantini, Marco ^a   Cocconcelli, Giuseppe ^c   Ghiron, Chiara ^c   Kalmar, Christopher L ^b   Singh, Natasha ^b   Merrick, Ellen C ^b   Patel, Manoj K ^b   Zuliani, Valentina ^a  

^a UNIVERSITY OF PARMA   (Italy)

^b UNIVERSITY OF VIRGINIA   (United States)

^c Siena Biotech SpA   (Italy)

Author keywords

Diarylimidazoles; Parallel synthesis; Sodium channel

Indexed keywords

2,4(5) DIARYLIMIDAZOLE DERIVATIVE; IMIDAZOLE DERIVATIVE; SODIUM CHANNEL BLOCKING AGENT; UNCLASSIFIED DRUG;

ARTICLE; BIOLOGICAL ACTIVITY; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; ELECTROPHYSIOLOGY; STRUCTURE ACTIVITY RELATION;

CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; IMIDAZOLES; ION CHANNEL GATING; MODELS, CHEMICAL; MOLECULAR STRUCTURE; NERVE TISSUE PROTEINS; PROTEIN ISOFORMS; SODIUM; SODIUM CHANNEL BLOCKERS; SODIUM CHANNELS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 53349164226     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.036     Document Type: Article

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11. 4 and the solvent was removed in vacuo. The isolation of the target compounds from the crude reaction mixture was obtained using SCX-2 column (2 g, 30-90 μm, loading 0.4 meq/g). The column is prewashed with DCM/methanol = 1:1 (10 mL), the side products were eluted with methanol (10 mL) and then the desired 2,4(5)-arylimidazoles were eluted with a methanolic ammonia 5% w/w solution (10 mL).
12. 2 5, Hepes 5, and glucose 5 (pH adjusted to 7.4 with NaOH). Compounds were prepared as 100 mM stock solutions in dimethyl sulfoxide (DMSO) and diluted to desired concentration in perfusion solution. The maximum DMSO concentration used was 0.3% and had no effect on current amplitude. All experiments were performed at room temperature (20-22 °C). After establishing whole-cell, a minimum series resistance compensation of 75% was applied. Sodium currents were elicited by a depolarizing step from a holding potential of -100 to +10 mV for a duration of 25 ms at 15 s intervals. Test compounds were applied after a 3 min control period and continued until a steady state current amplitude was observed. All data represents percentage mean block ± standard error of the mean (SEM).