1192256-10-2Relevant articles and documents
Process development of a novel azetidinyl ketolide antibiotic
Li, Bryan,Magee, Thomas V.,Buzon, Richard A.,Widlicka, Daniel W.,Bill, Dave R.,Brandt, Thomas,Cao, Xiaoping,Coutant, Michael,Dou, Haijian,Granskog, Karl,Flanagan, Mark E.,Hayward, Cheryl M.,Li, Bin,Liu, Fengwei,Liu, Wei,Nguyen, Thuy-Trinh,Raggon, Jeffrey W.,Rose, Peter,Rainville, Joseph,Reilly, Usa Datta,Shen, Yue,Sun, Jianmin,Wilcox, Glenn E.
, p. 788 - 797 (2012/08/27)
Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.
Discovery of azetidinyl ketolides for the treatment of susceptible and multidrug resistant community-acquired respiratory tract infections
Magee, Thomas V.,Ripp, Sharon L.,Li, Bryan,Buzon, Richard A.,Chupak, Lou,Dougherty, Thomas J.,Finegan, Steven M.,Girard, Dennis,Hagen, Anne E.,Falcone, Michael J.,Farley, Kathleen A.,Granskog, Karl,Hardink, Joel R.,Huband, Michael D.,Kamicker, Barbara J.,Kaneko, Takushi,Knickerbocker, Michael J.,Liras, Jennifer L.,Marra, Andrea,Medina, Ivy,Nguyen, Thuy-Trinh,Noe, Mark C.,Obach, R. Scott,O'Donnell, John P.,Penzien, Joseph B.,Reilly, Usa Datta,Schafer, John R.,Shen, Yue,Stone, Gregory G.,Strelevitz, Timothy J.,Sun, Jianmin,Tait-Kamradt, Amelia,Vaz, Alfin D. N.,Whipple, David A.,Widlicka, Daniel W.,Wishka, Donn G.,Wolkowski, Joanna P.,Flanagan, Mark E.
experimental part, p. 7446 - 7457 (2010/06/13)
Respiratory tract bacterial strains are becoming increasingly resistant to currently marketed macrolide antibiotics. The current alternative telithromycin (1) from the newer ketolide class of macrolides addresses resistance but is hampered by serious safe