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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2007-4-30
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pubmed:abstractText |
A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented.
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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 |
May
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:DuffyJoseph LJL,
pubmed-author:EiermannGeorge JGJ,
pubmed-author:HeHuaibingH,
pubmed-author:KirkBrian ABA,
pubmed-author:LeitingBarbaraB,
pubmed-author:LyonsKathryn AKA,
pubmed-author:PatelReshma ARA,
pubmed-author:PatelSangita BSB,
pubmed-author:PetrovAlexsandrA,
pubmed-author:ScapinGiovannaG,
pubmed-author:ThornberryNancy ANA,
pubmed-author:WangLipingL,
pubmed-author:WeberAnn EAE,
pubmed-author:WuJoseph KJK
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2879-85
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17350841-Administration, Oral,
pubmed-meshheading:17350841-Alanine,
pubmed-meshheading:17350841-Animals,
pubmed-meshheading:17350841-Binding Sites,
pubmed-meshheading:17350841-Biological Availability,
pubmed-meshheading:17350841-Crystallography, X-Ray,
pubmed-meshheading:17350841-Cyclohexanes,
pubmed-meshheading:17350841-Dipeptidyl Peptidase 4,
pubmed-meshheading:17350841-Dipeptidyl-Peptidase IV Inhibitors,
pubmed-meshheading:17350841-Enzyme Inhibitors,
pubmed-meshheading:17350841-Glucose Tolerance Test,
pubmed-meshheading:17350841-Mice,
pubmed-meshheading:17350841-Models, Molecular,
pubmed-meshheading:17350841-Molecular Structure,
pubmed-meshheading:17350841-Phenylalanine,
pubmed-meshheading:17350841-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. joseph_duffy@merck.com
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pubmed:publicationType |
Journal Article
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