【文章名】Synthesis and Antibacterial Activity of Novel Pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic Acid Derivatives Carrying the 3-Cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl Group as a C-10 Substituent.
Synthesis and Antibacterial Activity of Novel Pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic Acid Derivatives Carrying the 3-Cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl Group as a C-10 Substituent.
[摘要]：Novel pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid derivs. I (R1 = Me, CH2F; R2, R3 = H, Me, F) carrying a 3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl moiety at the C-10 position were synthesized and their in vitro antibacterial activity, i.v. single-dose toxicity, convulsion inductive ability, and phototoxicity were evaluated. It appeared evident that compds. I with cis-substituted pyrrolidinyl moiety (R3 = H) exhibited 2- to 16-fold more potent in vitro antibacterial activity than clinafloxacin against quinolone-resistant Gram-pos. clin. isolates. Furthermore, it was found that introduction of a fluorine atom to the C-4 position of the 3-cyclopropylaminomethyl-1-pyrrolidinyl moiety reduced i.v. single-dose acute toxicity and the convulsion inductive ability, and introduction of a fluorine atom to the C-3 Me group of the pyridobenzoxazine nucleus eliminated the phototoxicity.
