title: Design and synthesis of carborane-containing androgen receptor (AR) antagonist bearing a pyridine ring.
abstract: We previously developed carborane-containing potent AR antagonists, BA321 and BA341, on the basis of our hypothesis that the carborane cage would be an excellent hydrophobic pharmacophore in place of steroidal C and D rings. As an extension of that work, we designed and synthesized carborane-containing AR antagonist candidates with a pyridine ring. Compound 6b, which has a pyridine ring directly bound to the p-carborane cage at the 3-position, exhibited potent AR-antagonistic activity in transcriptional activation assay using NIH3T3 cells transfected with a hAR-expression plasmid. In addition, it showed more potent antiandrogenic activity than that of the well-known antiandrogen flutamide and comparable activity to that of (R)-bicalutamide in SC-3 cell proliferation assay.
authors: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors: Kiminori
authors: K
authors: Ohta
authors: Tokuhito
authors: T
authors: Goto
authors: Shinya
authors: S
authors: Fijii
authors: Tomoharu
authors: T
authors: Suzuki
authors: Shigeru
authors: S
authors: Ohta
authors: Yasuyuki
authors: Y
authors: Endo
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001880:Boranes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005485:Flutamide / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry*; D011944:Receptors, Androgen / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000494:pharmacology; D014162:Transfection
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D001880:Boranes; D009570:Nitriles; D011725:Pyridines; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D005485:Flutamide; C053541:bicalutamide; C023666:pyridine