Pyrolysis of the adduct of benzamide oxime and dimethyl acetylenedicarboxylate leads to 5,6‐dihydroxy‐2‐phenyl‐4‐pyrimidinecarboxylic acid methyl ester (4a) rather than 4,5‐dihydro‐α,4‐dioxo‐2‐phenyl‐1H‐imidazole‐5‐acetic acid, methyl ester (1).

A series of 5-amino- and 5-hydroxyquinolone antibacterials substituted at C7 with a select group of common piperazinyl and 3-aminopyrrolidinyl side chains was prepared. These 5-substituted derivatives were compared to the analogous 5-hydrogen compounds for antiinfective activity by using DNA gyrase inhibition, minimum inhibitory concentrations against a variety of bacteria, and in vivo efficacy in the mouse infection model. The influence on the structure-activity relationships of varied substituents at C8 (H, F, Cl) and N1 (ethyl, cyclopropyl, difluorophenyl) was also studied. The results showed that several of the structure-activity conclusions regarding side-chain bulk at C7, the effect of halogen at C8, and the effect of the C5-amino group were greatly influenced by the choice of the N1-substituent. Several outstanding broad spectrum quinolones were identified in this work. In particular, the spectrum and potency of the 7-piperazinyl quinolones could be greatly enhanced by the judicious choice of C5-, C8-, and N1-substituents.

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4‐Cyclopropyl‐5,7‐difluoro‐6‐(4‐methyl‐1‐piperazinyl)‐4H‐1,4‐benzothiazine‐2‐carboxylic acid 1‐oxide (2c) and 4‐cyclopropyl‐5,7‐difluoro‐6‐(4‐methyl‐1‐piperazinyl)‐4H‐1,4‐benzothiazine‐2‐carboxylic acid 1,1‐dioxide (2d) were prepared and assayed for antibacterial activity and inhibition of DNA gyrase.