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rdf:type |
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lifeskim:mentions |
umls-concept:C0001128,
umls-concept:C0166415,
umls-concept:C0205314,
umls-concept:C0243192,
umls-concept:C0441655,
umls-concept:C0679622,
umls-concept:C0935929,
umls-concept:C1552644,
umls-concept:C1554184,
umls-concept:C1823153,
umls-concept:C2349976
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pubmed:issue |
4
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pubmed:dateCreated |
2002-2-8
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pubmed:abstractText |
Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, Dietary,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Hypolipidemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylpropionates,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone,
http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:AndersenAnne-Sofie TAS,
pubmed-author:BrandChristian LCL,
pubmed-author:BuryPaul SPS,
pubmed-author:FlecknerJanJ,
pubmed-author:JeppesenLoneL,
pubmed-author:LehmannSøren VSV,
pubmed-author:MogensenJohn PJP,
pubmed-author:MortensenSteen BSB,
pubmed-author:PanajotovaVladimiraV,
pubmed-author:PetterssonIngridI,
pubmed-author:PolivkaZdenekZ,
pubmed-author:RasmussenHanne BHB,
pubmed-author:SauerbergPerP,
pubmed-author:SindelarKarelK,
pubmed-author:SturisJeppeJ,
pubmed-author:SvenssonL AndersLA,
pubmed-author:WöldikeHelle FHF,
pubmed-author:WassermannKarstenK,
pubmed-author:WulffErik MEM,
pubmed-author:YnddalLarsL
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
45
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
789-804
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11831892-Animals,
pubmed-meshheading:11831892-Blood Glucose,
pubmed-meshheading:11831892-Carbazoles,
pubmed-meshheading:11831892-Cholesterol,
pubmed-meshheading:11831892-Cholesterol, Dietary,
pubmed-meshheading:11831892-Crystallography, X-Ray,
pubmed-meshheading:11831892-Drug Evaluation, Preclinical,
pubmed-meshheading:11831892-Glucose Tolerance Test,
pubmed-meshheading:11831892-Hypoglycemic Agents,
pubmed-meshheading:11831892-Hypolipidemic Agents,
pubmed-meshheading:11831892-Male,
pubmed-meshheading:11831892-Mice,
pubmed-meshheading:11831892-Models, Molecular,
pubmed-meshheading:11831892-Nuclear Proteins,
pubmed-meshheading:11831892-Phenylpropionates,
pubmed-meshheading:11831892-Rats,
pubmed-meshheading:11831892-Rats, Sprague-Dawley,
pubmed-meshheading:11831892-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:11831892-Stereoisomerism,
pubmed-meshheading:11831892-Structure-Activity Relationship,
pubmed-meshheading:11831892-Thiazoles,
pubmed-meshheading:11831892-Thiazolidinediones,
pubmed-meshheading:11831892-Transcription Factors,
pubmed-meshheading:11831892-Triglycerides
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pubmed:year |
2002
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pubmed:articleTitle |
Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity.
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pubmed:affiliation |
Novo Nordisk A/S, Novo Nordisk Park E9 2.02, 2760 Måløv, Denmark. psa@novonordisk.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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