SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NOVEL PYRIDOBENZOXAZINE ANALOGS

A series of novel LVFX (7) analogues bearing 4,4-dialkyl-3-aminopyrrol idines at the C-10 position of pyridobenzoxazine was synthesized and t heir antibacterial activities, pharmacokinetics and acute toxicities i n animals were evaluated, Non-alkylated pyrrolidine derivative 26a sho wed greater activity than LVFX (7) against gram-positive and gram-nega tive bacteria including Pseudomonas aeruginosa, but 26a possessed high acute toxicity in mice and unfavorable pharmacokinetics in rats, When compared with 26a, 4,4-dialkylated derivatives 26c, e, g showed more potent activity against gram-positive bacteria along: with an improvem ent of pharmacokinetics and reduction of acute toxicity: Increases in lipophilicity by alkylation on the pyrrolidine ring resulted in a good influence on the above profiles.