Tumor necrosis factor-alpha production enhancing activity of substituted 3'-methylthalidomide: influence of substituents at the phthaloyl moiety on the activity and stereoselectivity.
The synthesis and tumor necrosis factor (TNF)-alpha production enhancing activity of substituted 3'-methylthalidomides on human leukemia cell line HL-60 stimulated with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) are described. Though the introduction of an electron-donating amino group at the phthaloyl moiety of alpha-methylthalidomides enhanced the activity, substituted alpha-methylthalidomides showed decreased stereoselectivity as compared to that of non-substituted alpha-methylthalidomide. The data indicates that the TNF-alpha production enhancing activity of thalidomide derivatives depends on both the electronic-state of substituents at the fused benzene ring and the stereochemistry of the glutarimide moiety.
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
H
H
Miyachi
Y
Y
Koiso
R
R
Shirai
S
S
Niwayama
J O
JO
Liu
Y
Y
Hashimoto
D018922:HL-60 Cells; D006801:Humans; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
C114058:3'-methylthalidomide; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide