Dicarba-closo-dodecaboranes as a pharmacophore. Retinoidal antagonists and potential agonists.

T Iijima, Y Endo, M Tsuji, E Kawachi, H Kagechika, K Shudo

文献索引：Chem. Pharm. Bull. 47(3) , 398-404, (1999)

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摘要

Synthesis and biological evaluation of the first dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Their retinoidal activity were examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for retinoic acid receptor (RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. The 4-carboranyl-substituted compounds (7, 11) showed antagonistic activity but no agonistic activity even in the presence of the potent synergist HX630. On the other hand, the 3-carboranyl-substituted compounds (8, 12) showed potential agonistic activity, but no antagonistic activity. The results indicates that carboranes are applicable as the hydrophobic moiety of biologically active molecules.