Magee, Thomas V.; Brown, Matthew F.; Starr, Jeremy T.; Ackley, David C.; Abramite, Joseph A.; Aubrecht, Jiri; Butler, Andrew; Crandon, Jared L.; Dib-Hajj, Fadia; Flanagan, Mark E.; Granskog, Karl; Hardink, Joel R.; Huband, Michael D.; Irvine, Rebecca; Kuhn, Michael; Leach, Karen L.; Li, Bryan; Lin, Jian; Luke, David R.; MacVane, Shawn H.; Miller, Alita A.; McCurdy, Sandra; McKim, James M.; Nicolau, David P.; Nguyen, Thuy-Trinh; Noe, Mark C.; O’Donnell, John P.; Seibel, Scott B.; Shen, Yue; Stepan, Antonia F.; Tomaras, Andrew P.; Wilga, Paul C.; Zhang, Li; Xu, Jinfeng; Chen, Jinshan Michael published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections》.Quality Control of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate The author mentioned the following in the article:
The authors report novel polymyxin analogs with improved antibacterial in vitro potency against polymyxin resistant recent clin. isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogs. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analog 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages. The experimental part of the paper was very detailed, including the reaction process of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate(cas: 77837-09-3Quality Control of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate)
Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate(cas: 77837-09-3) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. Quality Control of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylateThe lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds.