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Updated: Jun 1, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones
Andrea Fajdetić1, Adrijana Vinter, Hana Čipčić Paljetak
1GlaxoSmithKline Research Center Zagreb Ltd., Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. andrea.fajdetic@glpg.com
Abstract:
Synthesis, antibacterial activity and pharmacokinetic properties of a novel class of macrolide antibiotics-macrolones-derived from azithromycin, comprising oxygen atom(s) in the linker and either free or esterified quinolone 3-carboxylic group, are reported. Selected compounds showed excellent antibacterial potency towards key erythromycin resistant respiratory pathogens. However, the majority of compounds lacked good bioavailability. The isopropyl ester, compound 35, and a macrolone derivative with an elongated linker 29 showed the best oral bioavailability in rats, both accompanied with an excellent overall microbiology profile addressing inducible and constitutive MLSb as well as efflux mediated macrolide resistance in streptococci, while compound 29 is more potent against staphylococci.
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