139179-03-6Relevant articles and documents
Quinolizinone type compounds
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, (2008/06/13)
Antibacterial compounds having the formula STR1 and the pharmaceutically acceptable salts, esters and amides thereof, preferred examples of which include those compounds wherein A is =CR6 --; R1 is cycloalkyl of from three to eight carbon atoms or substituted phenyl; R2 is selected from the group consisting of STR2 R3 is halogen; R4 is hydrogen, loweralkyl, a pharmaceutically acceptable cation, or a prodrug ester group; R5 is hydrogen, loweralkyl, halo(loweralkyl), or --NR13 R14 ; and R6 is halogen, loweralkyl, halo(loweralkyl), hydroxy-substituted loweralkyl, loweralkoxy(loweralkyl), loweralkoxy, or amino(loweralkyl), as well as pharmaceutical compositions containing such compounds and the use of the same in the treatment of bacterial infections.
Synthesis and structure-activity relationships of 2-pyridones: A novel series of potent DNA gyrase inhibitors as antibacterial agents
Li, Qun,Chu, Daniel T. W.,Claiborne, Akiyo,Cooper, Curt S.,Lee, Cheuk M.,Raye, Kathleen,Berst, Kristine B.,Donner, Pamela,Wang, Weibo,Hasvold, Lisa,Fung, Anthony,Ma, Zhenkun,Tufano, Michael,Flamm, Robert,Shen, Linus L.,Baranowski, John,Nilius, Angela,Alder, Jeff,Meulbroek, Jonathan,Marsh, Kennan,Crowell, DeAnne,Hui, Yuhua,Seif, Louis,Melcher, Laura M.,Henry, Rodger,Spanton, Steven,Faghih, Ramin,Klein, Larry L.,Tanaka, S. Ken,Plattner, Jacob J.
, p. 3070 - 3088 (2007/10/03)
Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-a]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.
