Synthesis, Crystal Structure Analysis, and Pharmacological Characterization of Disila-bexarotene, a Disila-Analogue of the RXR-Selective Retinoid Agonist Bexarotene

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• 作者：Jü ; rgen O. Daiss ; Christian Burschka ; John S. Mills ; John G. Montana ; Graham A. Showell ; Ian Fleming ; Claudine Gaudon ; Diana Ivanova ; Hinrich Gronemeyer ; and Reinhold Tacke
• 刊名：Organometallics
• 出版年：2005
• 出版时间：June 20, 2005
• 年：2005
• 卷：24
• 期：13
• 页码：3192 - 3199
• 全文大小：344K
• 年卷期：v.24,no.13(June 20, 2005)
• ISSN：1520-6041

文摘

Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the RXR-selective retinoid agonist bexarotene (1a) leads to disila-bexarotene (1b). Compound 1b was synthesized in a multistep synthesis, starting from 1,2-bis(chlorodimethylsilyl)ethane. The identity of 1b was established by elemental analysesand multinuclear NMR studies, and the C/Si analogues 1a and 1b (and an intermediate inthe synthesis of 1b) were structurally characterized by single-crystal X-ray diffraction.Furthermore, 1a and 1b were studied for their interaction with retinoid X receptors. Althoughthe twofold sila-substitution of 1a resulted in significant differences in the molecularstructures of 1a and 1b, disila-bexarotene (1b) was shown to be a highly potent RXR agonist.