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Structural Development of Silicon-Containing Retinoids: Structure-Activity Relationship Study of the Hydrophobic
Tsuyoshi Oikawa1, Shinya Fujii1, Shuichi Mori1
1Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
Abstract:
We designed and synthesized a series of retinobenzoic acids bearing various silyl functionalities in order to explore in detail the structure-activity relationship (SAR) at the hydrophobic moiety of retinoids. Among the synthesized compounds, 24 c bearing a t-butyldimethylsilyl (TBS) group at the hydrophobic site exhibited potent retinoid activity comparable to that of the lead compound Am555S (4). Compound 24 c exhibited transcription-promoting activity towards all three subtypes of retinoic acid receptor (RAR), but showed the highest activity towards RARγ, in contrast to the high RARα-selectivity of Am80 (3) and Am555S (4). The SARs presented here should be helpful in the development of subtype-selective retinoids, and in particular 24 c might be a promising lead compound for new RARγ ligands.
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