A series of 3-O-phosphorylated analogs (4-10) of a novel bone-targeting estradiol analog (3) were synthesized after a thorough study of the reaction of 3 with a selection of phosphoryl chlorides under a variety of reaction conditions. Evaluation of these novel phosphate analogs for affinity for hydroxyapatite revealed that they bind with equal or higher affinity when compared to the bone tissue accumulator, tetracycline.
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