Low-Calcemic, Highly Antiproliferative, 23-Oxa Ether Analogs of the Natural Hormone 1,25-Dihydroxyvitamin D3: Design, Synthesis, and Preliminary Biological Evaluation

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• 作者：Kimberly S. Petersen ; Patrick M. Dolan ; Thomas W. Kensler ; Sara Peleg ; Gary H. Posner
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 15, 2007
• 年：2007
• 卷：50
• 期：23
• 页码：5824 - 5832
• 全文大小：132K
• 年卷期：v.50,no.23(November 15, 2007)
• ISSN：1520-4804

文摘

Eight new side-chain allylic, benzylic, and propargylic ether analogs of the natural hormone calcitriol havebeen rationally designed and easily synthesized. Three of these 23-oxa ether analogs lacking the typicalside-chain OH group are more antiproliferative in vitro and desirably less calcemic in vivo than the naturalhormone. One of these three 23-oxa analogs has transcriptional potency almost as high as that of calcitriol,even though it binds to the human vitamin D receptor only about 1% as well as calcitriol.