Synthesis and antibacterial activity of novel 15-membered macrolide derivatives: 4″-Carbamate, 11,12-cyclic carbonate-4″-carbamate and 11,4″-di-O-arylcarbamoyl analogs of azithromycin

Synthesis and antibacterial activity of novel 11,12-cyclic carbonate azithromycin 4″-O-carbamate derivatives

“…In contrast, almost all of the compounds with the C-4 00 prolonged side chains were less active against erythromycinsusceptible strains than the corresponding compounds with the C-4 00 short arylalkyl side chain in the published paper. 18 These results described above suggest that the prolonged side chain may further enhance the activity against erythromycin-resistant strains encoded by the erm gene or the erm and mef genes, but lose their activity against erythromycin-susceptible strains.…”

“…These compounds with prolonged side chains showed remarkably improved activity against strains encoded by the erm gene or the erm and mef genes, compared with the corresponding compounds with the C-4 00 short arylalkyl side chain reported by previously by us. 18 Compound 7b and 7d, especially, showed significant potent activity against erythromycin-resistant strains encoded by the erm gene and the erm and mef genes, respectively. In contrast, almost all of the compounds with the C-4 00 prolonged side chains were less active against erythromycinsusceptible strains than the corresponding compounds with the C-4 00 short arylalkyl side chain in the published paper.…”

“…17,18 In the published paper, 18 we reported that all of the tested compounds showed significantly potent activity (0.03-0.12 mg ml À1 ) against erythromycin-susceptible bacteria, and some of them showed potent activity (0.06-0.25 mg ml À1 ) against erythromycin-resistant S. pneumoniae A22072 encoded by the mef gene, compared with AZM or CAM. Particularly, the compounds with 4-fluorobenzyl, phenethyl or 3,4-methylenedioxyphenethyl groups at the C-4 00 position had the most potent activity against erythromycin-resistant S. pneumoniae A22072 encoded by the mef gene (0.06 mg ml À1 ).…”

“…15 In anticipation of inheriting its beneficial antibacterial and excellent pharmacokinetic profiles, we have recently reported the synthesis of novel 11,12-cyclic carbonate-4 00 -O-carbamate derivatives of AZM, which showed improved activity against erythromycin-resistant S. pneumoniae (Supplementary Materials). 17,18 These results prompted us to further explore modifications at the C-4 00 position of the cladinose of AZM.…”

Synthesis and antibacterial activity of novel 4″-carbamates of 6,11-di-O-methylerythromycin A

“…9 Compounds 5a and 5b ( Figure 3) were found to have potent activity against erythromycinresistant S. pneumoniae encoded by the erm or mef gene. 17,18 Compounds 6a and 6b ( Figure 3) are effective (0.5 and 0.5 mg ml À1 ) against two strains of erythromycin-resistant S. pneumoniae, whose resistance is encoded by the erm and mef gene, respectively. 19 6,11-Di-O-methylerythromycin A ( Figure 4, compound 7) shows excellent in vitro and in vivo antibacterial activity against Grampositive bacteria and Mycoplasma pneumoniae.…”