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A series of novel LVFX (7) analogues bearing 4,4-dialkyl-3-aminopyrrolidines at the C-10 position of pyridobenzoxazine was synthesized and their antibacterial activities, pharmacokinetics and acute toxicities in animals were evaluated. Non-alkylated pyrrolidine derivative 26a showed greater activity than LVFX (7) against gram-positive and gram-negative 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 improvement 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.
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
August 1998,
Bioorganic & medicinal chemistry letters,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
March 2002,
Bioorganic & medicinal chemistry letters,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
November 2006,
Bioorganic & medicinal chemistry,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
January 2008,
Bioorganic & medicinal chemistry letters,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
July 2006,
Bioorganic & medicinal chemistry letters,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
August 2004,
Archiv der Pharmazie,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
July 2013,
Bioorganic & medicinal chemistry letters,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
October 2018,
European journal of medicinal chemistry,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
January 2014,
Chemical & pharmaceutical bulletin,
K Kawakami, and
S Atarashi, and
Y Kimura, and
M Takemura, and
I Hayakawa
January 2011,
Chemical & pharmaceutical bulletin,
