Author/Authors :
Alexis Denis، نويسنده , , Constantin Agouridas، نويسنده , , Jean-Michel Auger، نويسنده , , Yannick Benedetti، نويسنده , , Alain Bonnefoy، نويسنده , , François Bretin، نويسنده , , Jean-François Chantot، نويسنده , , Arlette Dussarat، نويسنده , , Claude Fromentin، نويسنده , , Solange Gouin DʹAmbrières، نويسنده , , Sylvette Lachaud، نويسنده , , Patrick Laurin، نويسنده , , Odile Le Martret، نويسنده , , Véronique Loyau، نويسنده , , Nicole Tessot، نويسنده , , Jean-Marie Pejac، نويسنده , , Sébastien Perron، نويسنده ,
Abstract :
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 μg/ml, bioavailability=49%, AUC0–8 = 17.2 μg.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.
