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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2006-7-6
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pubmed:abstractText |
Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. Compound 1a inhibits insulin release in vitro and in vivo and preserves beta cell function in preclinical animal models suggesting that such a compound could find use in treatment or prevention of type 1 and type 2 diabetes. The crystal structure and a convergent synthesis of 1a are presented together with a range of new analogues of 1a. Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg). Structural modifications of this series of K(ATP) channel openers have provided compounds with promising pharmacokinetic properties indicating that brief periods of beta cell rest can be achieved.
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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 |
Jul
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:ArkhammarPer O GPO,
pubmed-author:BodvarsdottirThora BTB,
pubmed-author:BoonenHarrie C MHC,
pubmed-author:EbdrupSørenS,
pubmed-author:FremmingTinnaT,
pubmed-author:HansenJ BondoJB,
pubmed-author:JensenAnette FrostAF,
pubmed-author:KornøHanne THT,
pubmed-author:NielsenFlemming EFE,
pubmed-author:StidsenCarstenC,
pubmed-author:WahlPhilipP,
pubmed-author:WorsaaeAnneA,
pubmed-author:YnddalLarsL
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4127-39
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16821773-Animals,
pubmed-meshheading:16821773-Bicyclo Compounds, Heterocyclic,
pubmed-meshheading:16821773-Biological Availability,
pubmed-meshheading:16821773-Cell Line,
pubmed-meshheading:16821773-Crystallography, X-Ray,
pubmed-meshheading:16821773-Cyclic S-Oxides,
pubmed-meshheading:16821773-Female,
pubmed-meshheading:16821773-Humans,
pubmed-meshheading:16821773-Insulin,
pubmed-meshheading:16821773-Ion Channel Gating,
pubmed-meshheading:16821773-Islets of Langerhans,
pubmed-meshheading:16821773-Male,
pubmed-meshheading:16821773-Membrane Potentials,
pubmed-meshheading:16821773-Molecular Structure,
pubmed-meshheading:16821773-Muscle, Smooth,
pubmed-meshheading:16821773-Muscle Relaxation,
pubmed-meshheading:16821773-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:16821773-Radioligand Assay,
pubmed-meshheading:16821773-Rats,
pubmed-meshheading:16821773-Rats, Sprague-Dawley,
pubmed-meshheading:16821773-Rats, Wistar,
pubmed-meshheading:16821773-Rats, Zucker,
pubmed-meshheading:16821773-Structure-Activity Relationship,
pubmed-meshheading:16821773-Thiadiazines
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pubmed:year |
2006
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pubmed:articleTitle |
New 3-alkylamino-4H-thieno-1,2,4-thiadiazine 1,1-dioxide derivatives activate ATP-sensitive potassium channels of pancreatic beta cells.
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pubmed:affiliation |
Novo Nordisk Research and Development, Novo Nordisk Park, DK 2760 Måløv, Denmark.
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pubmed:publicationType |
Journal Article,
In Vitro
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