Synthesis and biological activities of 26-hydroxy-27-nor-derivatives of 1 alpha, 25-dihydroxyvitamin D3.
Starting with (20S)-20-(p-toluenesulfonyl)oxymethyl-pregna-1, 5-dien-3 alpha-ol (4), we synthesized three vitamin D analogs in 10 to 11 steps: 1 alpha, 26-dihydroxy-27-nor-vitamin D3 (1), its 3-epi analog (2), and 2 beta-methoxy-1 alpha, 26-dihydroxy-27-nor-vitamin D3 (3). We tested the derivatives in the murine mesenchymal cell line C3H1OT1/2. All substances were less potent in inhibition of cell proliferation, inhibition of adipocyte differentiation, and induction of gene activation, and had a lower affinity to the vitamin D receptor than the native vitamin D3 metabolite 1.25(OH)2D3. The affinity of 1 to the vitamin D binding protein was about three times higher than that of 1.25(OH)2D3.
Department of Gene Regulation and Differentiation, Association for Biotechnological Research, Braunschweig, Germany.
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Scheddin
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Mayer
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Wittmann
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Schönecker
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Gliesing
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Reichenbächer
D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D017930:Genes, Reporter; D051379:Mice; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014809:Vitamin D-Binding Protein / Q000378:metabolism
C104285:1,26-dihydroxy-27-norvitamin D3; C104286:2-methoxy-1,26-dihydroxy-27-norvitamin D3; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D015675:Osteocalcin; C055085:calcipotriene; D002762:Cholecalciferol; D015500:Chloramphenicol O-Acetyltransferase; D002117:Calcitriol