Original Article

The Journal of Antibiotics (2009) 62, 133–144; doi:10.1038/ja.2009.1; published online 13 February 2009

Synthesis and biological properties of 4"-O-acyl derivatives of 8a-Aza-8a-homoerythromycin

Vlado Stimac1, Sulejman Alihodzic1, Gorjana Lazarevski1, Stjepan Mutak1, Zorica Marusic Istuk1, Andrea Fajdetic1, Ivana Palej1, Hana Cipcic Paljetak1, Jasna Padovan1, Branka Tavcar1 and Vesna Erakovic Haber1

1GSK Research Centre Zagreb Ltd, Zagreb, Croatia

Correspondence: Dr V Stimac, GSK Research Centre Zagreb Ltd, Prilaz baruna Filipovica 29, Zagreb, Croatia. E-mail: vlado.z.stimac@gsk.com

Received 27 August 2008; Accepted 5 January 2009; Published online 13 February 2009.

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Abstract

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.

Keywords:

azalide, acylide, anti-bacterial activity, pharmacokinetics, structure-activity relationship

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