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Highly antiproliferative, low-calcemic, side-chain ketone analogs of the hormone 1alpha,25-dihydroxyvitamin D3
Gary H Posner1, Hyung Jin Kim, Mehmet Kahraman
1Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA. ghp@jhu.edu
Abstract:
A series 2a-4b of seven new side-chain ketone analogs of calcitriol (1) have been prepared. Unexpectedly, several of these 24- and 25-tert-butyl ketones, even though lacking the classical side-chain tertiary hydroxyl group, are considerably more antiproliferative in vitro than the hormone calcitriol (1) even at physiologically relevant low nanomolar concentrations and are less calcemic than calcitriol (1) in vivo. In addition, ketone analog 19-nor-2a is not significantly less calcemic in vivo than 19-methylene analog 2a.
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