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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2003-6-12
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pubmed:abstractText |
Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine (NVP-DPP728, 8c) to its follow-up, 1-[[(3-hydroxy-1-adamantyl) amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP-LAF237, 12j). The pharmacological profile of 12j in obese Zucker fa/fa rats along with pharmacokinetic profile comparison of 8c and 12j in normal cynomolgus monkeys is discussed. The results suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing excellent oral bioavailability and potent antihyperglycemic activity with potential for once-a-day administration.
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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 |
Jun
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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 |
19
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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 |
2774-89
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12801240-Adamantane,
pubmed-meshheading:12801240-Administration, Oral,
pubmed-meshheading:12801240-Animals,
pubmed-meshheading:12801240-Biological Availability,
pubmed-meshheading:12801240-Blood Glucose,
pubmed-meshheading:12801240-Caco-2 Cells,
pubmed-meshheading:12801240-Crystallography, X-Ray,
pubmed-meshheading:12801240-Diabetes Mellitus, Type 2,
pubmed-meshheading:12801240-Dipeptidyl Peptidase 4,
pubmed-meshheading:12801240-Enzyme Inhibitors,
pubmed-meshheading:12801240-Humans,
pubmed-meshheading:12801240-Hypoglycemic Agents,
pubmed-meshheading:12801240-Macaca fascicularis,
pubmed-meshheading:12801240-Male,
pubmed-meshheading:12801240-Pyrrolidines,
pubmed-meshheading:12801240-Rats,
pubmed-meshheading:12801240-Rats, Zucker,
pubmed-meshheading:12801240-Structure-Activity Relationship
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pubmed:year |
2003
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pubmed:articleTitle |
1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.
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pubmed:affiliation |
Novartis Institute for Biomedical Research, One Health Plaza, East Hanover, New Jersey 07936, USA. edwin.villhauer@pharma.novartis.com
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pubmed:publicationType |
Journal Article
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