title: Modulators of tumor necrosis factor alpha production bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Koiso
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
mesh_terms: 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
chemical_list: D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide