Modulators of tumor necrosis factor alpha production bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore.
Previous studies on the structural development of tumor necrosis factor alpha (TNF-alpha) production regulators derived from thalidomide (N-alpha-phthalimidoglutarimide) revealed that a hydrophobic substituent at the nitrogen atom of the phthalimide ring is critical for potent activity. We have designed and prepared phthalimide derivatives bearing a boron cluster, dicarba-closo-dodecaborane (carborane), which has a hydrophobic character and spherical geometry, as a novel candidate of biological response modifiers. These compounds were shown to regulate TNF-alpha production by HL-60 cells, as expected. The result provides a further example of the application of carborane as a hydrophobic pharmacophore of biologically active molecules.
Tsuji
M
M
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Koiso
Y
Y
Takahashi
H
H
Hashimoto
Y
Y
Endo
Y
Y
D004797:Enzyme-Linked Immunosorbent Assay; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide