Source:http://linkedlifedata.com/resource/pubmed/id/17110116
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-1-8
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pubmed:abstractText |
We have synthesized four new geometric isomers of 1alpha,25-dihydroxy-2-(2'-fluoroethylidene)-19-norvitamin D analogs 1 and 2 having a 20R- and 20S-configuration, whose structures are correlated with 2MD possessing high potencies in stimulating bone formation in vitro and in vivo. The E-isomers of (20R)- and (20S)-2-fluoroethylidene analogs 1a and 1b were comparable with the natural hormone 1alpha,25-(OH)(2)D(3) in binding to the vitamin D receptor (VDR), while two Z-isomers 2a and 2b were about 15-20 times less active than the hormone. In inducing expression of the vitamin D responsive element-based luciferase reporter gene, the E-isomers 1a and 1b were 1.2- and 8.6-fold more potent than the hormone, respectively, while the Z-isomers 2a and 2b had 27-55% of the potency. On the basis of the biological activities and a docking simulation based on X-ray crystallographic analysis of the VDR ligand-binding pocket, the structure-activity relationships of the fluorinated 19-norvitamin D analogs are discussed.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,25-dihydroxy-19-norvitamin D3,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Osteopontin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Spp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vinyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/vinyl fluoride
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0968-0896
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1475-82
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pubmed:meshHeading |
pubmed-meshheading:17110116-Animals,
pubmed-meshheading:17110116-Binding Sites,
pubmed-meshheading:17110116-COS Cells,
pubmed-meshheading:17110116-Calcitriol,
pubmed-meshheading:17110116-Cercopithecus aethiops,
pubmed-meshheading:17110116-Mice,
pubmed-meshheading:17110116-Osteopontin,
pubmed-meshheading:17110116-Protein Binding,
pubmed-meshheading:17110116-Rats,
pubmed-meshheading:17110116-Receptors, Calcitriol,
pubmed-meshheading:17110116-Structure-Activity Relationship,
pubmed-meshheading:17110116-Transcription, Genetic,
pubmed-meshheading:17110116-Vinyl Compounds,
pubmed-meshheading:17110116-Vitamin D Response Element
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pubmed:year |
2007
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pubmed:articleTitle |
Structure-activity relationships of 19-norvitamin D analogs having a fluoroethylidene group at the C-2 position.
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pubmed:affiliation |
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
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pubmed:publicationType |
Journal Article
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