Fluorine substitution can block CYP3A4 metabolism-dependent inhibition: Identification of (S)-N-[1-(4-fluoro-3-morpholin-4-ylphenyl)ethyl]-3-(4-fluorophenyl)acrylamide as an orally bioavailable KCNQ2 opener devoid of CYP3A4 metabolism-dependent inhibition

Journal of Medicinal Chemistry

Volumn 46, Issue 18, 2003, Pages 3778-3781

  Wu, Yong Jin ^a   Davis, Carl D ^a   Dworetzky, Steven ^a   Fitzpatrick, William C ^a   Harden, David ^a   He, Huan ^a   Knox, Ronald J ^a   Newton, Amy E ^a   Philip, Thomas ^a   Polson, Craig ^a   Sivarao, Digavalli V ^a   Sun, Li Qiang ^a   Tertyshnikova, Svetlana ^a   Weaver, David ^a   Yeola, Suresh ^a   Zoeckler, Mary ^a   Sinz, Michael W ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACRYLAMIDE; CYTOCHROME P450 3A4; FLUORINE; KETOCONAZOLE; N [1 (4 FLUORO 3 MORPHOLIN 4 YLPHENYL)ETHYL] 3 (4 FLUOROPHENYL)ACRYLAMIDE; RITONAVIR; UNCLASSIFIED DRUG;

ARTICLE; BIOAVAILABILITY; DEALKYLATION; DIALYSIS MEMBRANE; DRUG INHIBITION; DRUG METABOLISM; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME SPECIFICITY; HYDROXYLATION; LIVER MICROSOME; MICROSOME MEMBRANE; MINIMUM INHIBITORY CONCENTRATION; RECEPTOR BLOCKING;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; CELL LINE; CINNAMATES; CYTOCHROME P-450 ENZYME SYSTEM; DISEASE MODELS, ANIMAL; FLUORINE; INJECTIONS, INTRAVENOUS; ION CHANNEL GATING; KCNQ2 POTASSIUM CHANNEL; MALE; MEMBRANE POTENTIALS; MIGRAINE DISORDERS; MORPHOLINES; PARIETAL LOBE; PATCH-CLAMP TECHNIQUES; POTASSIUM CHANNELS; POTASSIUM CHANNELS, VOLTAGE-GATED; RATS; RATS, SPRAGUE-DAWLEY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0042921620     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm034111v     Document Type: Article

References (20)

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20. 2 also activated other members of the KCNQ family. Although these compounds activated these channels, further electrophysiological characterization is required.