Mitscher L A, Flynn D L, Gracey H E, Drake S D
J Med Chem. 1979 Nov;22(11):1354-7. doi: 10.1021/jm00197a014.
The synthesis and antimicrobial activity of the methylenedioxy positional isomers, 1-ethyl-1,4-dihydro-5,6-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (9) and 1-ethyl-1,4-dihydro-7,8-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (17), of oxolinic acid (18) have been accomplished. Isomer 9 was prepared by the reaction of N-ethyl-6,7-methylenedioxyisatoic anhydride with sodioethyl formylacetate [L. A. Mitscher, H. E. Gracey, G. W. Clark III, and T. Suzuki, J. Med. Chem., 21, 485 (1978)], while isomer 17 was prepared by thermal cyclization of diethyl 2-[(2,3-methylenedioxyanilino)methylene]malonate [D. Kaminsky and R. I. Meltzer, J. Med. Chem., 11, 160 (1968)]. Both of the new isomers are less active in vitro when compared to oxolinic acid (18) itself.
恶喹酸（18）的亚甲二氧基位置异构体，即1-乙基-1,4-二氢-5,6-亚甲二氧基-4-氧代-3-喹啉羧酸（9）和1-乙基-1,4-二氢-7,8-亚甲二氧基-4-氧代-3-喹啉羧酸（17）的合成及抗菌活性已完成。异构体9是通过N-乙基-6,7-亚甲二氧基异邻苯二甲酸酐与甲酰基乙酸钠反应制备的[L. A. 米切尔，H. E. 格雷西，G. W. 克拉克三世，以及铃木彻，《药物化学杂志》，21，485（1978）]，而异构体17是通过2-[(2,3-亚甲二氧基苯胺基)亚甲基]丙二酸二乙酯的热环化反应制备的[D. 卡明斯基和R. I. 梅尔策，《药物化学杂志》，11，160（1968）]。与恶喹酸（18）本身相比，这两种新异构体在体外的活性都较低。
