Novel pyrido[1,2,3- de][1,4]benzoxazine-6-carboxylic acid derivatives 5- 9 carrying a 3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl moiety at the C-10 position were synthesized and their in vitro antibacterial activity, intravenous single-dose toxicity, convulsion inductive ability, and phototoxicity were evaluated. It appeared evident that compounds 5a, 6a, 8a, and 9a, which have a cis-oriented 4-methyl or 4-fluoro-3-cyclopropylaminomethyl-1-pyrrolidinyl moiety at the C-10 position, exhibited 2- to 16-fold more potent in vitro antibacterial activity than clinafloxacin against quinolone-resistant Gram-positive clinical isolates. Furthermore, it was obvious that introduction of a fluorine atom to the C-4 position of the 3-cyclopropylaminomethyl-1-pyrrolidinyl moiety reduced intraveneous single-dose acute toxicity and the convulsion inductive ability, and introduction of a fluorine atom to the C-3 methyl group of the pyridobenzoxazine nucleus eliminated the phototoxicity.

中文翻译：

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带有3-环丙基氨基甲基-4-取代的-1-吡咯烷基作为C-10取代基的新型吡啶并[1,2,3-de] [1,4]苯并恶嗪-6-羧酸衍生物的合成和抗菌活性。

合成了在C-10位带有3-环丙基氨基甲基-4-取代的-1-吡咯烷基基团的新型吡啶并[1,2,3-de] [1,4]苯并恶嗪-6-羧酸衍生物5-9评估了体外抗菌活性，静脉内单剂量毒性，惊厥诱导能力和光毒性。似乎明显的是，在C-10位具有顺式4-甲基或4-氟-3-环丙基氨基甲基-1-吡咯烷基基团的化合物5a，6a，8a和9a表现出2至16倍的折叠比克林沙星对喹诺酮耐药的革兰氏阳性临床分离株具有更强的体外抗菌活性。此外，