title: Design and synthesis of novel androgen receptor antagonists with sterically bulky icosahedral carboranes.
abstract: Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable chemical and thermal stability, and hydrophobic character. These features may allow application of carboranes as a new hydrophobic core structure in biologically active molecules that interact hydrophobically with receptors. Here, we report the design and synthesis of novel androgen antagonists bearing a carborane moiety. These compounds, particularly 8a, 8c, and 9d, exhibited anti-androgenic activity similar to that of the well-known anti-androgen flutamide in reporter gene assay using NIH3T3 cells transfected with a human AR expression plasmid. The carborane cage seems to be a privileged hydrophobic pharmacophore for the expression of AR-antagonistic activity.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Aoba-ku, Sendai, Japan.
authors.forename: Tokuhito
authors.initials: T
authors.lastname: Goto
authors.forename: Kiminori
authors.initials: K
authors.lastname: Ohta
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism; D015195:Drug Design; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D011944:Receptors, Androgen / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen; D013196:Dihydrotestosterone