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

摘要

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.