Novel 8a-aza-8a-homoerythromycin--4''-(3-substituted-amino)propionates with broad spectrum antibacterial activity.
Fifteen-membered 8a-aza-8a-homoerythromycins derived from either erythromycin or clarithromycin have been acylated to form 4''-O-propenoyl derivative. These functionalized analogues underwent Michael reaction with primary or secondary amines to afford novel 8a-aza-8a-homoerythromycin-4''-(3-substituted-amino)propionates. This preparative sequence was adapted so that analogues could be made by parallel synthesis. Among them, 4-quinolone derivatives show particularly good antibacterial potency against macrolide resistant bacteria, comparable or better than azithromycin and telithromycin.
Hutinec
Antun
A
GlaxoSmithKline Research Centre, Zagreb, Prilaz baruna Filipovića 29, HR-10 000 Zagreb, Croatia. antun.z.hutinec@gsk.com
Derek
Marko
M
Lazarevski
Gorjana
G
Sunjić
Vitomir
V
Paljetak
Hana Cipcić
HC
Alihodzić
Sulejman
S
Eraković Haber
Vesna
V
Dumić
Miljenko
M
Marsić
Natasa
N
Mutak
Stjepan
S
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D004917:Erythromycin