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Recent Developments of 2–Substituted Analogs of 1,25(OH)2D3

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The plethora of biological activities of 1,25(OH)2D3 and its analogs suggests an enormous potential for vitamin D therapy in the treatment of hyperproliferative diseases (cancer, psoriasis), endocrine dysfunction (hyperparathyroidism), immune disorders (autoimmune diseases, transplant rejection), bone disorders (osteoporosis, Paget's bone disease). However, the therapeutic limitation of 1,25(OH)2D3 is its calcemic and phosphatemic activities, since it can cause serious side effects such as hypercalcemia and hyperphosphatemia at super physiological levels. Therefore, numerous efforts have been made to find the new vitamin D analogs, that retain the therapeutically important properties of 1,25(OH)2D3 but with greater selectivity, which allows more effective intervention with fewer toxic side effects. This review will focus on the biological activities of the 2–substituted analogs of 1,25(OH)2D3. They were classified as 2α–, 2β–, 2,2–disubstituted analogs, and those with modifications in both the A–ring at the 2–position and the side chains. Their structure–activity relationships and binding features with the vitamin D receptor (VDR) were discussed.
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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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