Synthesis and Antibacterial Activity of a Novel Series of Acylides:  3-O-(3-Pyridyl)acetylerythromycin A Derivatives

Abstract

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.

Azalides from Azithromycin to New Azalide Derivatives

“…A similar 3-O-(3-pyridyl)-acetyl derivative (78) (Fig. 18) of 8 was prepared [83], but antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae was lower than with the corresponding 14-membered derivative; only activity against H. influaenzae was improved.…”

Antibacterial Activity of Novel Sulfonylureas, Ureas and Thioureas of 15-Membered Azalides

“…The discovery of highly potent representatives of the third-generation of macrolides, like ketolides (Agouridas 1998), acylides (Tanikawa et al 2001;Tanikawa et al 2003), anhydrolides (Elliott et al 1998), etc., was a step forward to tackle the efflux problems Pestka & LeMahieu 1974a& 1974bPestka et al 1976;Allen. 1977;Van Bambeke et al 2008)' to (Tanikawa et al, 2001;Tanikawa et al, 2003), anhydrolides (Elliott et al, 1998), etc., was a step forward to tackle the efflux problems Pestka & LeMahieu 1974a& 1974bPestka et al, 1976;Allen.…”

“…1977;Van Bambeke et al 2008)' to (Tanikawa et al, 2001;Tanikawa et al, 2003), anhydrolides (Elliott et al, 1998), etc., was a step forward to tackle the efflux problems Pestka & LeMahieu 1974a& 1974bPestka et al, 1976;Allen. 1977;Van Bambeke et al, 2008).…”

In Vitro and In Vivo Activities of the Novel Ketolide RBx 14255 against Clostridium difficile

“…Ketolides belong to a novel class of macrolide antibiotics with improved antibacterial activity against macrolide-resistant organisms (17). In this study, we have investigated for the first time the activity of RBx 14255, a novel ketolide (Fig.…”

“…In summary, we have investigated and reported the activity of RBx 14255, a novel ketolide, against anaerobic bacteria for the first time. It was found that RBx 14255 is active against erythromycinand clarithromycin-resistant C. difficile strains, including the epidemic BI/NAP1/027 strain, and several bacterial species with different resistance patterns; these findings could indicate a special advantage of RBx 14255 over existing macrolides and ketolides (15,17). RBx 14255 is a novel antibacterial agent that prevents the growth of C. difficile by inhibiting protein synthesis and could be investigated for C. difficile treatment.…”