Vancomycin disulfide derivatives as antibacterial agents

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 3, 2004, Pages 735-738

  Mu, YongQi ^a   Nodwell, Matthew ^a   Pace, John L ^a   Shaw, Jeng Pyng ^a   Judice, J Kevin ^a,b  

^a THERAVANCE INC   (United States)

^b GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; DISULFIDE; DRUG METABOLITE; LIPID; VANCOMYCIN;

ANIMAL EXPERIMENT; ARTICLE; CHEMICAL BOND; CONTROLLED STUDY; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG ACTIVITY; DRUG DESIGN; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG POTENCY; DRUG SYNTHESIS; KIDNEY PARENCHYMA; LIVER; MALE; NONHUMAN; RAT;

EID: 1642452636     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.11.040     Document Type: Article

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16. 3 (1 mmol, 1 equiv) in methanol (5 mL) was added to the reaction, followed by 3 mmol TFA, and stirring was continued for an additional h. The reaction mixture was concentrated and then precipitated in acetonitrile. Purification on RP-HPLC gave the desired product as a TFA salt.
17. MIC was determined against clinical isolates of MRSA (ATCC 33591), MSSA (ATCC 13709) and vancomycin resistant Enterococcus faecium (KPB-01) and E. faecalis (MGH-01) of Van A and Van B (ATCC 51575) phenotype utilizing the NCCLS broth microdilution method. Bactericidal activity was evaluated by time-kill analysis.
18. Calculation was based on the peak area ratio of metabolite peak versus parent peak.