Antibacterial oxazolidinones possessing a novel C-5 side chain. (5R)-trans-3-[3-fluoro-4-(1-oxotetrahydrothiopyran-4-yl)phenyl] -2-oxooxazolidine-5-carboxylic acid amide (PF-00422602), a new lead compound

Journal of Medicinal Chemistry

Volumn 50, Issue 24, 2007, Pages 5886-5889

  Poel, Toni Jo ^a   Thomas, Richard C ^a   Adams, Wade J ^a   Aristoff, Paul A ^a   Barbachyn, Michael R ^a   Boyer, Frederick E ^a   Brieland, Joan ^a   Brideau, Roger ^a   Brodfuehrer, Joanne ^a   Brown, Alan P ^a   Choy, Allison L ^a   Dermyer, Michael ^a   Dority, Michael ^a   Ford, Charles W ^a   Gadwood, Robert C ^a   Hanna, Debra ^a   Hongliang, Cai ^a   Huband, Michael D ^a   Huber, Christopher ^a   Kelly, Rose ^a   Kim, Ji Young ^a   Martin Jr , Joseph P ^a   Pagano, Paul J ^a   Ross, Daniel ^a   Skerlos, Laura ^a   Sulavik, Mark C ^a   Zhu, Tong ^a   Zurenko, Gary E ^a   Vara Prasad, J V N ^a   more..

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [3 FLUORO 4 (1 OXOTETRAHYDROTHIOPYRAN 4 YL)PHENYL] 2 OXOOXAZOLIDINE 5 CARBOXYLIC ACID AMIDE; AMINE OXIDASE (FLAVIN CONTAINING); BACTERIAL PROTEIN; BEFLOXATONE; BENZENE DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; FLUORINE DERIVATIVE; LINEZOLID; OXAZOLIDINE DERIVATIVE; OXAZOLIDINONE DERIVATIVE; PF 00422602; THIOPYRAN DERIVATIVE; TOLOXATONE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BONE MARROW TOXICITY; CONTROLLED STUDY; DISTRIBUTION VOLUME; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; ENTEROCOCCUS FAECALIS; ENTEROCOCCUS FAECIUM; ENZYME INHIBITION; FEMALE; IN VIVO STUDY; INFECTION; MALE; MOUSE; NONHUMAN; PROTEIN SYNTHESIS INHIBITION; RAT; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE;

ACETAMIDES; ADMINISTRATION, ORAL; ANIMALS; ANTI-BACTERIAL AGENTS; BIOLOGICAL AVAILABILITY; CYCLIC S-OXIDES; DOGS; DRUG RESISTANCE, BACTERIAL; FEMALE; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; INJECTIONS, INTRAVENOUS; MALE; MICE; MICROBIAL SENSITIVITY TESTS; MONOAMINE OXIDASE INHIBITORS; OXAZOLIDINONES; RATS; RATS, SPRAGUE-DAWLEY; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; STREPTOCOCCAL INFECTIONS; STREPTOCOCCUS PYOGENES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 37849012704     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070708p     Document Type: Article

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21. Data not shown.
22. Incubations were performed in duplicate with 0.03-0.2 mg/mL human liver microsomes, substrate (30 μM phenacetin for CYP 1A2, 7.5 μM diclofenac for CYP 2C9, 50 μM phenacetin for CYP 2C19, 10 μM dextromethorphan for CYP 2D6, 50 μM phenacetin, 50 μM midazolam, 1.5 μM felodipine for CYP 3A4), 1 mM NADPH, and in the presence of a positive control (furafylline for CYP1A2, sulfaphenazole for CYP 2C9, ticlopidine for CYP 2C19, quinidine for CYP 2D6, ketoneconazole and midazolam for CYP 3A4) or drug in 50 mM potassium phosphate buffer at pH 7.4. The concentrations of drug were 0, 1, 3, 7.5, 15, 40, 100, 500, and 1000 μM. The reactions were quenched with 500 μL of 100 ng/mL acetonitrile (ice-cold) after 7-30 min. The samples were analyzed by LC/MS after centrifugation.