Anti-HIV-1 activities and pharmacokinetics of new arylpiperazinyl fluoroquinolones.
Anti-HIV-1 activities and pharmacokinetics of a series of novel arylpiperazinyl fluoroquinolones are reported. Modification at the C-8 position with a trifluoromethyl group was superior to that with a difluoromethoxy group to achieve higher anti-HIV-1 activity. Two compounds studied exhibited quite high anti-HIV-1 activities (IC(50)<50 nM) in vitro and high bioavailabilities (BA>90%) in monkeys.
Ohmine
Toshinori
T
Biological Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, 140-8710, Tokyo, Japan.
Katsube
Tetsushi
T
Tsuzaki
Yasunori
Y
Kazui
Miho
M
Kobayashi
Nobuhiro
N
Komai
Tomoaki
T
Hagihara
Masahiko
M
Nishigaki
Takashi
T
Iwamoto
Aikichi
A
Kimura
Tomio
T
Kashiwase
Hiroto
H
Yamashita
Makoto
M
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D005617:Chlorofluorocarbons, Methane / Q000737:chemistry; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D008252:Macaca fascicularis; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D005617:Chlorofluorocarbons, Methane; D024841:Fluoroquinolones; C009554:fluoroform