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rdf:type |
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lifeskim:mentions |
umls-concept:C0166415,
umls-concept:C0205460,
umls-concept:C0220781,
umls-concept:C0243192,
umls-concept:C0678594,
umls-concept:C1175029,
umls-concept:C1552644,
umls-concept:C1823153,
umls-concept:C1880022,
umls-concept:C1883254,
umls-concept:C2349976
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pubmed:issue |
8
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pubmed:dateCreated |
2003-4-3
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pubmed:abstractText |
A new and improved synthesis of the peroxisome proliferator-activated receptor (PPAR) agonist ragaglitazar applicable for large-scale preparation has been developed. The convergent synthetic procedure was based on a novel enzymatic kinetic resolution step. The conformation of ragaglitazar bound to the hPPARgamma receptor was quite different compared to the single-crystal structures of the l-arginine salt of ragaglitazar. In particular, the phenoxazine ring system had varying orientations. Ragaglitazar had high affinity for the hPPARalpha and -gamma receptors with IC(50) values of 0.98 and 0.092 microM, respectively. The lack of hPPARdelta activity could be explained by the absence of binding in the tail-up pocket in the hPPARdelta receptor, in contrast to the hPPARdelta agonist GW2433, which was able to bind in both the tail-up and tail-down pockets of the receptor.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1306-17
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:12672231-Binding Sites,
pubmed-meshheading:12672231-Crystallography, X-Ray,
pubmed-meshheading:12672231-Hypoglycemic Agents,
pubmed-meshheading:12672231-Ligands,
pubmed-meshheading:12672231-Models, Molecular,
pubmed-meshheading:12672231-Oxazines,
pubmed-meshheading:12672231-Phenylpropionates,
pubmed-meshheading:12672231-Radioligand Assay,
pubmed-meshheading:12672231-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12672231-Stereoisomerism,
pubmed-meshheading:12672231-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar.
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pubmed:affiliation |
Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. sebd@novonordisk.com
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pubmed:publicationType |
Journal Article
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