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Abstract: A series of 3-keto-6-O-carbamoyl-11,12-cyclic thiocarbamate erythromycin A derivatives has been synthesized. The best compounds in this series possess potent in vitro antibacterial activity against erythromycin-susceptible and erythromycin-resistant bacteria. [Copyright &y& Elsevier]

Abstract: A novel series of ketolides containing heteroaryl groups that are linked to the erythronolide ring via a C6-carbazate functionality has been successfully synthesized. Careful modulation of the heteroaryl groups, the length and degree of saturation of the C6-carbazate linker, and the substituents present on each of the carbazate nitrogens led to compounds with potent activity against key bacterial respiratory pathogens. The best analogs of this series had in vitro and in vivo (sc dosing) profiles that were comparable to telithromycin. [Copyright &y& Elsevier]

Abstract: A new series of erythromycin A derivatives, the 6-O-heteroarylcarbamoyl-11,12-lactoketolides, with activity against macrolide-resistant streptococci, are described. Structurally, these macrolide antibiotics are characterized by a heteroaryl side chain attached to the macrolactone core through a carbamate linkage at the C6 position, as well as 11,12-γ-lactone and 3-keto functionalities. The synthesis and antibacterial activity of this new series of ketolides are discussed. [Copyright &y& Elsevier]

Abstract: Novel C6-carbamate ketolides with C2-fluorination and C9-oximation have been synthesized. The best compounds in this series displayed MIC values of 0.03–0.12μg/mL against streptococci containing erm and mef resistance determinants and 2–4μg/mL against Haemophilus influenzae. Several compounds also showed measurable activity against erm(B)-containing enterococci with MIC values of 2–8μg/mL. In vivo activity was adversely affected by fluorination, possibly as a result of increased serum protein binding. [Copyright &y& Elsevier]

A new series of antibacterial ketolides is reported, which features the use of a C-6 carbamate for tethering the arylalkyl sidechain to the macrolide core. The best members of this series display in vitro and in vivo activity comparable to telithromycin. Partial epimerization at C-2, unobserved in previously reported ketolides, was noted for this series. [Copyright &y& Elsevier]