Synthesis and antibacterial activity of 6-O-arylpropargyl-9-oxime-11,12- carbamate ketolides

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 10, 2004, Pages 2417-2421

  Beebe, Xenia ^a   Yang, Fan ^a   Bui, Mai H ^a   Mitten, Michael J ^a   Ma, Zhenkun ^a   Nilius, Angela M ^a   Djuric, Stevan W ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Antibacterial; Ketolides; Macrolides

Indexed keywords

ANTIINFECTIVE AGENT; CARBAMIC ACID DERIVATIVE; KETOLIDE; MACROLIDE;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; ARYLATION; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; IN VITRO STUDY; NONHUMAN;

ANIMALS; ANTI-BACTERIAL AGENTS; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, BACTERIAL; HAEMOPHILUS INFLUENZAE; KETOLIDES; MACROLIDES; RATS; RESPIRATORY TRACT INFECTIONS; STAPHYLOCOCCUS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 1942502755     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.03.020     Document Type: Article

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20. 50 ) to yield a 2 or 3 log reduction in bacteria count compared to vehicle-treated infected controls was calculated from the group means using linear regression. Percent responder was calculated from animals showing a 3 log reduction in organisms compared to the control mean.
21. 2 [pH=7.2 at rt]). Fibers were stimulated using platinum electrodes located in the chamber floor and impaled with 3 M KCl-filled microelectrodes, recorded digitally and analyzed using pClamp software. Studies were initiated after a minimum 30-min equilibration period with stimulation. Fibers were sequentially exposed to three ascending drug concentrations. The protocol consisted of pacing in a control (drug-free) solution for 20-25 min at a basic cycle length (BCL) of 2 s, and then consecutively paced at 800 ms BCL (75 bpm) during the transition to a 400 ms BCL for 2-3 min at each stimulation rate. Action potentials recorded at the end of each 25-min equilibration period were used to define drug effects and generate cumulative concentration-response curves.