3-Amino-1,5-benzodiazepinones: Potent, state-dependent sodium channel blockers with anti-epileptic activity

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 6, 2008, Pages 1963-1966

  Hoyt, Scott B ^a   London, Clare ^a   Wyvratt, Matthew J ^a   Fisher, Michael H ^a   Cashen, Doreen E ^a   Felix, John P ^a   Garcia, Maria L ^a   Li, Xiaohua ^a   Lyons, Kathryn A ^a   Euan MacIntyre, D ^a   Martin, William J ^a   Priest, Birgit T ^a   Smith, McHardy M ^a   Warren, Vivien A ^a   Williams, Brande S ^a   Kaczorowski, Gregory J ^a   Parsons, William H ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Epilepsy; Nav1; Sodium channel blocker

Indexed keywords

1' (6 CYANO 1,2,3,4 TETRAHYDRO 2 NAPHTHYL) 3,4 DIHYDRO 6 METHANESULFONAMIDOSPIRO[2H 1 BENZOPYRAN 2,4' PIPERIDIN] 4 OL; BENZODIAZEPINE DERIVATIVE; CARBAMAZEPINE; LAMOTRIGINE; MK 0499; POTASSIUM CHANNEL BLOCKING AGENT; SODIUM CHANNEL BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG STRUCTURE; DRUG SYNTHESIS; EPILEPSY; MEMBRANE POTENTIAL; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTICONVULSANTS; BENZODIAZEPINONES; ELECTROPHYSIOLOGY; ELECTROSHOCK; EPILEPSY; ETHER-A-GO-GO POTASSIUM CHANNELS; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMANS; MICE; MOLECULAR STRUCTURE; RATS; SODIUM CHANNEL BLOCKERS;

EID: 40749113547     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.01.123     Document Type: Article

References (20)

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17. Rat PK experiments were conducted as follows: test compounds were typically formulated as 1.5 mg/mL solutions in mixtures of PEG300/water or DMSO/PEG300/water. Fasted male Sprague-Dawley rats were given either a 1.0 mg/kg iv dose of test compound solution via a cannula implanted in the femoral vein (n = 3) or a 3.0 mg/kg po dose by gavage (n = 3). Serial blood samples were collected at 5 (iv only), 15, and 30 min, and at 1, 2, 4, 6, and 8 h post-dose. Plasma was collected by centrifugation, and plasma concentrations of test compound were determined by LC-MS/MS following protein precipitation with acetonitrile.
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