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

publication · 8 years ago
by Kimberly S. Petersen, Patrick M. Dolan, Thomas W. Kensler, Sara Peleg, Gary H. Posner (Johns Hopkins University)
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Eight new side-chain allylic, benzylic, and propargylic ether analogs of the natural hormone calcitriol have been rationally designed and easily synthesized. Three of these 23-oxa ether analogs lacking the typical side-chain OH group are more antiproliferative in vitro and desirably less calcemic in vivo than the natural hormone. 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.
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