Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones as Kv1.5 channel blockers for the treatment of atrial fibrillation

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 17, 2006, Pages 4629-4632

  Blass, Benjamin E ^a   Coburn, Keith ^a   Lee, Wenlin ^a   Fairweather, Neil ^a   Fluxe, Andrew ^a   Wu, Shengde ^a   Janusz, John M ^a   Murawsky, Michael ^a   Fadayel, Gina M ^a   Fang, Bin ^a   Hare, Michelle ^a   Ridgeway, Jim ^a   White, Ron ^a   Jackson, Chris ^a   Djandjighian, Laurent ^a   Hedges, Richard ^a   Wireko, Fred C ^a   Ritter, Amanda L ^a  

^a PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

Author keywords

1,2,3 Triazole; Atrial fibrillation; Kv1.5 ion channel

Indexed keywords

1,2,3 TRIAZOLE DERIVATIVE; CALCIUM CHANNEL L TYPE; POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KV1.5; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; HEART ATRIUM FIBRILLATION; IC 50; MOUSE; NONHUMAN; PATCH CLAMP; REFRACTORY PERIOD; SWINE;

ATRIAL FIBRILLATION; CELL LINE; CRYSTALLOGRAPHY, X-RAY; HUMANS; KV1.5 POTASSIUM CHANNEL; METHANE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; POTASSIUM CHANNEL BLOCKERS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33746222969     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.06.001     Document Type: Article

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21. 2, 10 mM Hepes, and 10 mM glucose, adjusted to pH 7.4 with NaOH. Series resistance was compensated following rupture of the seal. Currents were sampled at 1 KHz and filtered at 500 Hz. Cells were pulsed (0.2 Hz) to +60 mV for 1 s, from a holding potential of -70 mV. After stable control currents were obtained, inhibitors were perfused onto the cells at increasing concentrations until maximal inhibition was obtained for a given concentration. Whole-cell patch-data were analyzed using Clampfit 8.0 in pCLAMP software (Axon Instruments). IC50 values for compounds were determined by nonlinear regression analysis using GraphPad Prism software (San Diego,CA). Single point screening determinations were determined by comparing control current amplitudes at the end of the depolarizing pulses to maximally inhibited current amplitudes at inhibitor concentrations of 1 μM.