Successful application of serum shift prediction models to the design of dual targeting inhibitors of bacterial gyrase B and topoisomerase IV with improved in vivo efficacy

Bioorganic and Medicinal Chemistry Letters

Volumn 24, Issue 9, 2014, Pages 2177-2181

  Perola, Emanuele ^a   Stamos, Dean ^a   Grillot, Anne Laure ^a   Ronkin, Steven ^a   Wang, Tiansheng ^a   Letiran, Arnaud ^a   Tang, Qing ^a   Deininger, David D ^a   Liao, Yusheng ^a   Tian, Shi Kai ^a   Drumm, Joseph E ^a   Nicolau, David P ^b   Tessier, Pamela R ^b   Mani, Nagraj ^a   Grossman, Trudy H ^a   Charifson, Paul S ^a  

^a VERTEX PHARMACEUTICALS   (United States)

^b HARTFORD HOSPITAL   (United States)

Author keywords

Antibacterial; Gyrase B; Predictive models; Protein binding; Serum shift; Topoisomerase IV

Indexed keywords

ANTIINFECTIVE AGENT; DNA TOPOISOMERASE (ATP HYDROLYSING) B; DNA TOPOISOMERASE IV; DNA TOPOISOMERASE IV INHIBITOR; GYRASE B INHIBITOR; GYRASE INHIBITOR; UNCLASSIFIED DRUG; ANTIBIOTIC AGENT; BACTERIAL ENZYME; BENZIMIDAZOLE DERIVATIVE; BENZODIAZEPINE; DNA TOPOISOMERASE INHIBITOR; HUMAN SERUM ALBUMIN; LINEZOLID; PLASMA PROTEIN; WARFARIN; DNA TOPOISOMERASE (ATP HYDROLYSING);

ANTIBACTERIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; COLONY FORMING UNIT; DRUG CLEARANCE; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HUMAN; HYDROPHOBICITY; IN VIVO STUDY; LIPOPHILICITY; MINIMUM INHIBITORY CONCENTRATION; NONBIOLOGICAL MODEL; NONHUMAN; PROTEIN BINDING; SERUM SHIFT PREDICTION MODEL; SINGLE DRUG DOSE; STREPTOCOCCUS PNEUMONIA; STREPTOCOCCUS PNEUMONIAE; SUPPORT VECTOR MACHINE; ANIMAL EXPERIMENT; ANIMAL MODEL; BACTERIAL INFECTION; BINDING SITE; ENZYME INHIBITION; MODEL; PREDICTION; RAT; SERUM; SERUM SHIFT; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; ANIMAL; ANTAGONISTS AND INHIBITORS; BACTERIAL INFECTIONS; BACTERIUM; BLOOD; CHEMISTRY; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; MICROBIOLOGY;

BACTERIA (MICROORGANISMS); RATTUS;

ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIA; BACTERIAL INFECTIONS; BLOOD PROTEINS; DNA GYRASE; DNA TOPOISOMERASE IV; HUMANS; RATS; TOPOISOMERASE II INHIBITORS;

EID: 84899059625     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.03.022     Document Type: Article

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