Novel tethers in ketolide antibiotics

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 18, 2007, Pages 5049-5053

  Kaneko, Takushi ^a   Romero, Karina ^a   Li, Bryan ^a   Buzon, Richard ^a  

^a PFIZER INC   (United States)

Author keywords

Antibacterial; Curtius rearrangement; Dicarbamoyl methylene; Haemophillus influenzae; Ketolide; Linker; Streptococcus pneumoniae; Streptococcus pyogenes; Telithromycin

Indexed keywords

CARBAMIC ACID DERIVATIVE; KETOLIDE; MACROLIDE; TELITHROMYCIN; UREA DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ARTICLE; CHEMICAL REACTION; CONTROLLED STUDY; CURTIUS REARRANGEMENT; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; GERBIL; MINIMUM INHIBITORY CONCENTRATION; MOUSE; NONHUMAN; OTITIS MEDIA; STREPTOCOCCUS PNEUMONIAE; STREPTOCOCCUS PYOGENES; STRUCTURE ACTIVITY RELATION;

ANTI-BACTERIAL AGENTS; KETOLIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

STREPTOCOCCUS PNEUMONIAE; STREPTOCOCCUS PYOGENES;

EID: 34547900256     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.07.018     Document Type: Article

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17. Compounds 16 and 17 were prepared in the same way as compounds 13 except starting with a β-alanine adduct.
18. 4) δ ppm 0.85 (t, J = 7.05 Hz, 3H) 0.98 (d, J = 6.64 Hz, 3H) 1.09-1.32 (m, 13H) 1.46 (br s, 1H) 1.52 (s, 3H) 1.58 (br s, 1H) 1.65 (s, 2H) 1.71 (s, 2H) 1.97 (br s, 2H) 2.52 (s, 3H) 2.64 (d, J = 11.20 Hz, 1H) 2.77 (s, 4H) 3.20 (d, J = 6.64 Hz, 1H) 3.37-3.56 (m, 4H) 3.67 (br s, 1H) 4.06 (d, J = 9.54 Hz, 1H) 4.37 (d, J = 6.64 Hz, 1H) 4.77 (br s, 1H) 4.95 (br s, 1H) 5.12 (br s, 1H) 5.30 (d, J = 12.03 Hz, 2H) 7.04 (br s, 1H) 7.92 (s, 1H) 8.04 (br s, 1H) 8.10 (d, J = 8.29 Hz, 1H) 8.42 (s, 1H) 8.86 (d, J = 3.73 Hz, 2H); MS 846 (M+1).
19. Protective dose; dose that protects 50% of infected, treated animals.
20. Efficacious dose; the dose that cleared 50% of infected, treated animals.