Abstract: By the method of AM1, quantum chemistry indexes of 16 compounds of quinoline, 1,8naphthyridine and pyrido(2,3-C)pyridazine analogues were calculated and 4 QSAR equations were obtained. The results showed that the net charge of 4-carbonyl oxygen is highly correlated with the antibacterial activity in vitro, the correlation coefficient of the regressions are high(R≥0.96). The antibacterial activity in vitro is strongly influenced by the coplanarity of 3-carboxylic acid and the parent nucleus. In light of this study, a new parent nucleus of isothiazoleannexed quinolizine was proposed, which is expected to have much higher activity.