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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2009-9-14
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pubmed:abstractText |
Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.
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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 |
1464-3405
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pubmed:author |
pubmed-author:AhlijanianMichael KMK,
pubmed-author:CookJames MJM,
pubmed-author:GantThomasT,
pubmed-author:HelalChristopher JCJ,
pubmed-author:HoseaNatalieN,
pubmed-author:KangZhijunZ,
pubmed-author:KellyKristinK,
pubmed-author:LucasJohn CJC,
pubmed-author:MennitiFrank SFS,
pubmed-author:MenteScotS,
pubmed-author:PanditJayJ,
pubmed-author:RichterKarl E GKE,
pubmed-author:SchachterJoel BJB
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5703-7
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pubmed:meshHeading |
pubmed-meshheading:19700321-Alzheimer Disease,
pubmed-meshheading:19700321-Animals,
pubmed-meshheading:19700321-Binding Sites,
pubmed-meshheading:19700321-Caco-2 Cells,
pubmed-meshheading:19700321-Crystallography, X-Ray,
pubmed-meshheading:19700321-Cyclin E,
pubmed-meshheading:19700321-Cyclin-Dependent Kinase 2,
pubmed-meshheading:19700321-Cyclin-Dependent Kinase 5,
pubmed-meshheading:19700321-Drug Design,
pubmed-meshheading:19700321-Humans,
pubmed-meshheading:19700321-Imidazoles,
pubmed-meshheading:19700321-Mice,
pubmed-meshheading:19700321-Mice, Knockout,
pubmed-meshheading:19700321-Nerve Tissue Proteins,
pubmed-meshheading:19700321-Protein Kinase Inhibitors,
pubmed-meshheading:19700321-Structure-Activity Relationship
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pubmed:year |
2009
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pubmed:articleTitle |
Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease.
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pubmed:affiliation |
Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. chris.j.helal@pfizer.com
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pubmed:publicationType |
Journal Article
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