Synthesis and biological properties of 4''-O-acyl derivatives of 8a-Aza-8a-homoerythromycin.
A series of 4''-O-acyl derivatives of 8a-aza-8a-homoerythromycins A were synthesized and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent anti-bacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin-resistant Gram-positive pathogens. These compounds show moderate to high clearance and low oral bioavailability in preliminary in vivo pharmacokinetic studies in rat.
Stimac
Vlado
V
GSK Research Centre Zagreb Ltd, Zagreb, Croatia. vlado.z.stimac@gsk.com
Alihodzic
Sulejman
S
Lazarevski
Gorjana
G
Mutak
Stjepan
S
Istuk
Zorica Marusic
ZM
Fajdetic
Andrea
A
Palej
Ivana
I
Paljetak
Hana Cipcic
HC
Marsic
Natasa
N
Padovan
Jasna
J
Tavcar
Branka
B
Erakovic Haber
Vesna
V
D000215:Acylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002384:Catalysis; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C544242:8a-aza-8a-homoerythromycin; D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D004917:Erythromycin