title: Antioxidative activities of novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter.
abstract: 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.
authors.affiliation: POLA Chemical Industries, Inc., Pharmaceutical R&D Laboratories, 560 Kashio-cho, Totsuka-ku, Yokohama, Kanagawa 244-0812, Japan. m-kimura@pola.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Kimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Masuda
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawakatsu
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kubota
authors.forename: Masaki
authors.initials: M
authors.lastname: Mitani
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kishii
authors.forename: Masato
authors.initials: M
authors.lastname: Inazu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kiuchi
authors.forename: Katsuji
authors.initials: K
authors.lastname: Oguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Namiki
mesh_terms: 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
chemical_list: D000975:Antioxidants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines