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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2006-10-12
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pubmed:abstractText |
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.
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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 |
Oct
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BallaronStephen JSJ,
pubmed-author:BenoDavid W ADW,
pubmed-author:BhagavatulaLakshmiL,
pubmed-author:DjuricStevan WSW,
pubmed-author:FickesMichael GMG,
pubmed-author:FryerRyan MRM,
pubmed-author:Kempf-GroteAnita JAJ,
pubmed-author:KopeckaHanaH,
pubmed-author:LiXiaofengX,
pubmed-author:LongMichelle AMA,
pubmed-author:LongeneckerKenton LKL,
pubmed-author:LubbenThomas HTH,
pubmed-author:MadarDavid JDJ,
pubmed-author:McDermottToddT,
pubmed-author:MikaAmanda KAK,
pubmed-author:PeiZhonghuaZ,
pubmed-author:PirehDaisyD,
pubmed-author:PolakowskiJamesJ,
pubmed-author:ReinhartGlenn AGA,
pubmed-author:RichardsSteven JSJ,
pubmed-author:SegretiJasonJ,
pubmed-author:ShamHing LHL,
pubmed-author:StashkoMichael AMA,
pubmed-author:StewartKent DKD,
pubmed-author:TrevillyanJames MJM,
pubmed-author:Von GeldernThomas WTW,
pubmed-author:WellsHeidiH,
pubmed-author:WiedemanPaul EPE,
pubmed-author:WittenbergerStevenS,
pubmed-author:YongHongH,
pubmed-author:ZinkerBradley ABA
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pubmed:issnType |
Print
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pubmed:day |
19
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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 |
6416-20
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17034148-Adenosine Deaminase,
pubmed-meshheading:17034148-Adenosine Deaminase Inhibitors,
pubmed-meshheading:17034148-Administration, Oral,
pubmed-meshheading:17034148-Animals,
pubmed-meshheading:17034148-Binding Sites,
pubmed-meshheading:17034148-Caco-2 Cells,
pubmed-meshheading:17034148-Crystallography, X-Ray,
pubmed-meshheading:17034148-Diabetes Mellitus, Type 2,
pubmed-meshheading:17034148-Dipeptidyl Peptidase 4,
pubmed-meshheading:17034148-Dipeptidyl-Peptidase IV Inhibitors,
pubmed-meshheading:17034148-Dogs,
pubmed-meshheading:17034148-Female,
pubmed-meshheading:17034148-Glucose Intolerance,
pubmed-meshheading:17034148-Glycoproteins,
pubmed-meshheading:17034148-Humans,
pubmed-meshheading:17034148-Hypoglycemic Agents,
pubmed-meshheading:17034148-Macaca fascicularis,
pubmed-meshheading:17034148-Models, Molecular,
pubmed-meshheading:17034148-Molecular Structure,
pubmed-meshheading:17034148-Pyridines,
pubmed-meshheading:17034148-Pyrrolidines,
pubmed-meshheading:17034148-Rats,
pubmed-meshheading:17034148-Rats, Sprague-Dawley,
pubmed-meshheading:17034148-Rats, Zucker,
pubmed-meshheading:17034148-Stereoisomerism,
pubmed-meshheading:17034148-Structure-Activity Relationship
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pubmed:year |
2006
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pubmed:articleTitle |
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.
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pubmed:affiliation |
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064-6001, USA. david.madar@abbott.com
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pubmed:publicationType |
Journal Article
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