Synthetic analogues of vitamin D3 with an oxygen atom in the side chain skeleton A trial of the development of vitamin D compounds which exhibit potent differentiation‐inducing activity without inducing hypercalcemia

摘要

>Four analogues of vitamin D₃ with an oxygen atom in the side chain skeleton were synthesized to determine whether their differentiation-inducing activity could be separated structurally from their activity to induce hypercalcemia. The order of the in vitro potency to reduce nitroblue tetrazolium in human myeloid leukemia cells (HL-60) was 22-oxa-1α25-(OH)₂D₃ 1α,25-(OH)₂D₃ 20-oxa-1α,25-(OH)₂D₃≒22-oxa-1α-(OH) D₃ 1α-(OH)D₃ 20-oxa-1α-(OH)D₃. 22-Oxa-1α,25-(OH)₂D₃, was also about 10-times more potent than 1α,25-(OH)₂D₃ in suppressing proliferation and inducing differentiation of mouse myelomonocytic leukemia cells (WEHI-3), but the former was much weaker than the latter in inducing the release of 45Ca from prelabeled fetal mouse calvaria. These results suggest that the differentiation-inducing activity of vitamin D compounds can be separated structurally from their activity to induce hypercalcemia.