[Gyrase inhibitors. 3. Synthesis and reactions of 1,4-dihydro-4-oxo-(1)benzothieno(3,2-b)pyridin-3-carboxylic acid esters].
The title compound 4a is synthesized from potassium 3-aminobenzo[b]thiophene-2-carboxylate (1) by Gould-Jacobs reaction. Compound 4a reacts with alkyl halides and sodium hydride in DMF to yield the N-alkylpyridones 5a-c as well as the 4-alkoxypyridines 6a-c; with phosphoryl chloride the 4-chloropyridine 7a is obtained. The carboxylic acids 4b, 5d, 5e, 6d and 7b are received by alkaline saponification of the esters 4a, 5a-c, 6a-c and 7a. The carbinoles 8 and 9, formed by boranate reduction of the esters 6a and 7a, are transformed to the aldehydes 10 and 11 by activated manganese dioxide oxidation. The aldoxime 12 from the carbaldehyde 11 is dehydrated to yield the nitrile 13. The carbaldehyde 11 reacts with methyl beta-aminocrotonate to yield the 1,4-dihydropyridine (DHP) 14, which is dehydrogenated to give the 3,4'-bipyridine 15. The pyridone 4a reacts with tosylisocyanate to yield the 4-tosylaminopyridine 16a. The antibacterial activity of the carboxylic acids 4b, 5d, 5e and 6d is proved. The growth of Escherichia coli and Bacillus megaterium is inhibited by 5d in the same range as nalidixic acid does.
Görlitzer
K
K
Institut für Pharmazeutische Chemie, Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Kramer
C
C
Boyle
C
C
D001419:Bacteria / Q000187:drug effects; D002708:Chlorella / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D005658:Fungi / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D011725:Pyridines; D013876:Thiophenes; D059005:Topoisomerase II Inhibitors