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Denis, A. et al.

Denis, Agouridas, Auger, Benedetti, Bonnefoy, Bretin, Chantot, Dussarat, Fromentin, D'Ambrières, Lachaud, Laurin, Le Martret, Loyau, Tessot, Pejac, Perron,

Synthesis and antibacterial activity of HMR 3647 a new ketolide highly potent against erythromycin-resistant and susceptible pathogens.

In the search for new ketolides with improved activities against erythromycin-resistant S. pneumoniae and H. influenzae we synthesized a new 11,12 carbamate ketolide substituted by an imidazo-pyridyl side chain: HMR 3647. This compound demonstrated a potent activity against erythromycin susceptible and resistant pathogens, including penicillin G/erythromycin A-resistant S. pneumoniae and H. influenzae. In vivo, HMR 3647 displayed good pharmacokinetic parameters (Cmax = 2.9 microg/ml, bioavailability=49%, AUC0.8 = 17.2 microg.h/l, t1/2=1h) and was shown to have a high therapeutic efficacy in mice infected by various respiratory pathogens, including multi-resistant S. pneumoniae and Gram negative bacteria such as H. influenzae. HMR 3647 appears to be a very promising agent for the treatment of respiratory infections and is currently in clinical trials.[1]

References

Synthesis and antibacterial activity of HMR 3647 a new ketolide highly potent against erythromycin-resistant and susceptible pathogens. Denis, A., Agouridas, C., Auger, J.M., Benedetti, Y., Bonnefoy, A., Bretin, F., Chantot, J.F., Dussarat, A., Fromentin, C., D'Ambrières, S.G., Lachaud, S., Laurin, P., Le Martret, O., Loyau, V., Tessot, N., Pejac, J.M., Perron, S. Bioorg. Med. Chem. Lett. (1999) [Pubmed]

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