Thienopyridinone antibacterials:: Synthesis and antibacterial activity of some 7-aryl-2-chloro-4,7-dihydro-4-oxothieno[2,3-b]pyridine-5-carboxylic acids

A series of 7-aryl-4-oxothieno[2,3-D]pyridine-5-carboxylic acids 8 and their methyl esters 7 were synthesized by intramolecular cyclization of the respective 3-N-arylamino-2-(2,5-dichloro-3-thenoyl) acrylates 6. The latter are accessible from methyl 3-ethoxy-2-(2,5-dichloro-3-thenoyl) acrylate 5 which, in turn, is obtained via the parent beta-keto ester 4. Of the present series, the 7-(p-hydroxyphenyl) and 7-(2',4'-difluorophenyl) derivatives 8e,i possess the highest activity especially against Klebsiella pneumoniae,Escherichia coli and Staphylococcus aureus (MICs of 8e/8i approximate to 0.06:0.25, 0.5:1.0 and 1.0:2.0 mu g/mL, respectively). (C) Elsevier, Paris.