Synthetic studies of vitamin D analogues. X. Synthesis and biological activities of 1 alpha,25-dihydroxy-21-norvitamin D3.
1 alpha,25-Dihydroxy-21-norvitamin D3 (3) was synthesized from 1 alpha-hydroxydehydroepiandrosterone (4). Certain biological properties of 3 were examined in comparison with those of 1 alpha,25-dihydroxyvitamin D3 (1) and 1 alpha,25-dihydroxy-21-nor-20-oxavitamin D3 (2) to evaluate the effect of the 21-methyl substituent on biological activities. The differentiation-inducing activity of 3 towards human myeloid leukemia cells was approximately one-fifth of that of 1, while in the binding affinity with chick intestinal cytosolic receptor, 3 was about one-tenth of that of 1. The rather weak effect of 3 on serum calcium levels in normal mice at a dosage of 500 micrograms/kg (intravenous administration) indicates that the essential importance of the 21-methyl moiety may lie in its effect on the regulation of calcium metabolism.
Kubodera
N
N
Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Miyamoto
K
K
Matsumoto
M
M
Kawanishi
T
T
Ohkawa
H
H
Mori
T
T
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000097:blood* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000737:chemistry; D007951:Leukemia, Myeloid / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C075166:1,25-dihydroxy-21-nor-20-oxavitamin D3; C075165:1,25-dihydroxy-21-norvitamin D3; C075167:1-hydroxydehydroepiandrosterone; D003687:Dehydroepiandrosterone; D002117:Calcitriol; D002118:Calcium