4''-O-(omega-Quinolylamino-alkylamino)propionyl derivatives of selected macrolides with the activity against the key erythromycin resistant respiratory pathogens.
Four macrolides-6-O-methyl-8a-aza-8a-homoerythromycin, clarithromycin, azithromycin and azithromycin 11,12-cyclic carbonate, have been selected for the construction of a series of new quinolone derivatives. The quinolone moiety is connected to the macrolide scaffold via a diaminoaklyl 4''-O-propionyl ester chain of varying length. At the terminus the linker is attached via one of the nitrogen atoms in the linker at C(6) or C(7) of the quinolone. Many of compounds described, particularly clarithromycin derivative 37, and azithromycin derivatives 48 and 55, exhibited excellent antibacterial activity against a wide range of clinically relevant macrolide-resistant organisms, with profiles superior to that of telithromycin, an enhanced spectrum ketolide.
Fajdetić
A
A
GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. andrea.z.fajdetic@gsk.com
Cipcić Paljetak
H
H
Lazarevski
G
G
Hutinec
A
A
Alihodzić
S
S
Derek
M
M
Stimac
V
V
Andreotti
D
D
Sunjić
V
V
Berge
J M
JM
Mutak
S
S
Dumić
M
M
Lociuro
S
S
Holmes
D J
DJ
Marsić
N
N
Eraković Haber
V
V
Spaventi
R
R
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011422:Propionates / Q000737:chemistry
D000900:Anti-Bacterial Agents; D018942:Macrolides; D011422:Propionates; D004917:Erythromycin