1.[Synthesis and transformations of ethyl 1,4-dihydro-4-oxo(1)benzofuro(3,2-b)pyridine-3-carboxylic acid esters: new antibacterial agents].
Görlitzer K1, Kramer C, Boyle C. Pharmazie. 2000 Sep;55(9):651-8.
The title compound 7 was synthesized from potassium 3-amino-benzofuran-2-carboxylate (1) by Gould-Jacobs-reaction. The pyridone 7 reacted with ethyl iodide by N- and O-alkylation to give 9 and 10, while methyl iodide only yielded the N-methylpyridone 11. The 4-chloropyridine 15 was obtained by heating 7 in phosphoryl chloride. Alkaline saponification of the esters 7, 9-11 and 15 afforded the carboxylic acids 8, 12-14 and 16. The carbaldehydes 19 and 22 were prepared from the ethylesters 10 and 15 by boranate reduction to the carbinoles 17 and 20 followed by dehydrogenation with activated manganese dioxide. The aldehyde 22 reacted with beta-aminocrotonic acid esters to yield the 1,4 dihydropyridines (DHP) 23. The pyridines 24 were formed by chemical or electrochemical dehydrogenation of the DHP 23. The tetrazole 27 was accessible from the aldehyde 22 via the aldoxime 25 and the nitrile 26. The pyridone 7 reacted with tosylisocyanate to yield the 4-tosylaminopyridine 28, which after alkylation to form 29 followed by detosylation to give 30 and subsequent alkaline hydrolysis produced the 4-aminonicotinic acid 31.
2.Interactions of metal ions with two quinolone antimicrobial agents (cinoxacin and ciprofloxacin). Spectroscopic and X-ray structural characterization. Antibacterial studies.
López-Gresa MP1, Ortiz R, Perelló L, Latorre J, Liu-González M, García-Granda S, Pérez-Priede M, Cantón E. J Inorg Biochem. 2002 Sep 30;92(1):65-74.
Several novel metal-quinolone compounds have been synthesized and characterized by analytical, spectroscopic and X-ray diffraction methods. The crystal structure of the four compounds, Na(2)[(Cd(Cx)3)(Cd(Cx)3(H2O))].12H2O, [Co(Cp)2(H2O)2].9H2O, [Zn(Cp)2(H2O)2].8H2O and [Cd(HCp)2(Cl)2].4H2O, is presented and discussed: HCx=1-ethyl-1,4-dihydro-4-oxo(1,3)-dioxolo(4,5-g)cinnoline-3-carboxylic acid and HCp=1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid. In all these compounds the quinolone acts as a bidentate chelate ligand that binds through one carboxylate oxygen atom and the exocyclic carbonyl oxygen atom. Complexes of ciprofloxacin were screened for their activity against several bacteria, showing activity similar to that of the ligand. In addition, the number of bacteria killed after 3 h of incubation with the ligand, [Co(Cp)2(H2O)2].9H2O, Ni(Cp)2.10H2O and Cu(Cp)2.6H2O, was determined against S. aureus ATCC25923.
3.[Potential antiallergic agents--synthesis and reactions of 1,4-dihydro-4-oxo-(1)benzofuro(3,2-b)pyridin-2-carboxylic acid esters].
Görlitzer K1, Kramer C. Pharmazie. 2000 Aug;55(8):587-94.
The title compounds 5 were received from the saponification of ethyl 3-aminobenzo[b]furan-2-carboxylate (3) followed by reaction with acetylenedicarboxylic diesters. The esters 5 reacted with alkyl iodides to give mixtures of the 4-alkoxypyridines 8 and the N-alkylpyridones 9. Alkaline hydrolysis of the esters 5, 8 and 9 yielded the carboxylic acids 6, 11 and 12. The carboxylic acid 6 could be decarboxylated to afford the annulated pyridone 7. The tetrazoles 21 and 22 were synthesized starting from the esters 8 and 9. At first, reduction afforded carbinoles, subsequent selective oxidation yielded the aldehydes 15 and 16, which were converted into aldoximes. Dehydration of the aldoximes formed nitriles, which added hydrazoic acid. The carbaldehydes 15 and 16 reacted in the Hantzsch-Synthesis with beta-aminocrotonic acid esters to form the 1,4-dihydropyridines (DHP) 23 and 24, which could be dehydrogenated to obtain the pyridines 25 and 26.