Antioxidative activities of novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter.
A new series of diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter (DAT), which were modified at both the diphenylalkyl moiety and the phenyl ring in the phenylamino moiety of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine 1, was evaluated for their inhibitory activities against auto-oxidative lipid peroxidation in canine brain homogenates. Some of these were approximately equivalent in activity to alpha-tocopherol as a potent antioxidant with IC(50) values of low micromolar order, and the 4-hydroxyphenyl derivative 11 showed the most potent antioxidative activity with an IC(50) value of 0.32 microM, exhibiting approximately 5-fold more potent activity than alpha-tocopherol. The structure-activity relationship (SAR) studies of the antioxidative activity of these derivatives are presented.
Kimura
Makoto
M
POLA Chemical Industries, Inc., Pharmaceutical R&D Laboratories, 560 Kashio-cho, Totsuka-ku, Yokohama, Kanagawa 244-0812, Japan. m-kimura@pola.co.jp
Masuda
Tomoko
T
Yamada
Koji
K
Kawakatsu
Nobuyuki
N
Kubota
Nobuo
N
Mitani
Masaki
M
Kishii
Kenichi
K
Inazu
Masato
M
Kiuchi
Yuji
Y
Oguchi
Katsuji
K
Namiki
Takayuki
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004285:Dogs; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines