Synthesis and preliminary chemotherapeutic evaluation of the fully C-linked glucuronide of N-(4-hydroxyphenyl)retinamide

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• 作者：Joel R. Walker ; Galal Alshafie ; Nirca Nieves ; Jamie Ahrens ; Margaret Clagett-Dame ; Hussein Abou-Issa and Robert W. Curley ; Jr.
• 关键词：Retinoids ; Carbon-linked glucuronide ; Chemoprevention ; Chemotherapy ; Breast cancer ; Synthesis
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2006
• 出版时间：1 May 2006
• 年：2006
• 卷：14
• 期：9
• 页码：3038-3048
• 全文大小：246 K

文摘

All-trans retinoic acid analogues such as N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive and chemotherapeutic agents but their utility has been hampered by dose-limiting side effects. The glucuronide derivatives of 4-HPR, the oxygen-linked 4-HPROG and the carbon-linked 4-HPRCG, have been found to be more effective agents. The synthetic route to the fully C-linked analogue of 4-HPROG (4-HBRCG), which employs Suzuki coupling and Umpolung chemistries as key methodologies, is shown. The results of this study show 4-HBRCG to be an effective chemotherapeutic agent in a rat mammary tumor model while being devoid of classical retinoid toxicities.