Synthetic studies of vitamin D analogues. XVII. Synthesis and differentiation-inducing activity of 1 alpha,24-dihydroxy-22-oxavitamin D3 analogues and their 20(R)-epimers.
Four vitamin D3 analogues, 1 alpha,24(S)- and 1 alpha,24(R)-dihydroxy-22-oxavitamin D3 (5 and 6) and their 20(R)-epimers (7 and 8) were synthesized from the 20(S)-alcohol (10). In tests of activity to induce differentiation of human myeloid leukemia cells (HL-60) to macrophages, 5 showed comparable activity to 1 alpha,25-dihydroxy-22-oxavitamin D3 (OCT) (2), and the other three analogues (6, 7 and 8) were less active than OCT (2). The binding properties of these analogues to the chick embryonic intestinal 1 alpha,25-dihydroxyvitamin D3 (1) receptor were evaluated. Furthermore, 20(R)-OCT (9) was synthesized and its biological properties were compared with those of OCT(2) and the 20(R)-epimers (7 and 8).
Kubodera
N
N
Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Watanabe
H
H
Miyamoto
K
K
Matsumoto
M
M
Matsuoka
S
S
Kawanishi
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D007951:Leukemia, Myeloid / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D002117:Calcitriol; C051883:maxacalcitol