|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
18
|
|
pubmed:dateCreated |
2001-8-24
|
|
pubmed:abstractText |
The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-aminopyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0022-2623
|
|
pubmed:author |
pubmed-author:AbramsMM,
pubmed-author:BellI MIM,
pubmed-author:BeshoreD CDC,
pubmed-author:BuserC ACA,
pubmed-author:CulbersonJ CJC,
pubmed-author:DavidsDD,
pubmed-author:Ellis-HutchingsMM,
pubmed-author:FernandesCC,
pubmed-author:GallicchioS NSN,
pubmed-author:GibbsJ BJB,
pubmed-author:GrahamS LSL,
pubmed-author:HartmanG DGD,
pubmed-author:HeimbrookD CDC,
pubmed-author:HomnickC FCF,
pubmed-author:HuffJ RJR,
pubmed-author:KassahunKK,
pubmed-author:KoblanK SKS,
pubmed-author:KohlN ENE,
pubmed-author:LobellR BRB,
pubmed-author:LyonsK RKR,
pubmed-author:MillerP APA,
pubmed-author:OmerC ACA,
pubmed-author:RodriguesA DAD,
pubmed-author:WalshE SES,
pubmed-author:WilliamsT MTM
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
30
|
|
pubmed:volume |
44
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2933-49
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:11520202-Alkyl and Aryl Transferases,
pubmed-meshheading:11520202-Animals,
pubmed-meshheading:11520202-Antineoplastic Agents,
pubmed-meshheading:11520202-Binding, Competitive,
pubmed-meshheading:11520202-Binding Sites,
pubmed-meshheading:11520202-Biological Availability,
pubmed-meshheading:11520202-Cell Line, Transformed,
pubmed-meshheading:11520202-Dogs,
pubmed-meshheading:11520202-Drug Design,
pubmed-meshheading:11520202-Drug Screening Assays, Antitumor,
pubmed-meshheading:11520202-Enzyme Inhibitors,
pubmed-meshheading:11520202-Farnesyltranstransferase,
pubmed-meshheading:11520202-Genes, ras,
pubmed-meshheading:11520202-Imidazoles,
pubmed-meshheading:11520202-Lactams,
pubmed-meshheading:11520202-Mice,
pubmed-meshheading:11520202-Mice, Transgenic,
pubmed-meshheading:11520202-Models, Molecular,
pubmed-meshheading:11520202-Neoplasms, Experimental,
pubmed-meshheading:11520202-Nitriles,
pubmed-meshheading:11520202-Pyrrolidinones,
pubmed-meshheading:11520202-Radioligand Assay,
pubmed-meshheading:11520202-Stereoisomerism,
pubmed-meshheading:11520202-Structure-Activity Relationship
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Design and biological activity of (S)-4-(5-([1-(3-chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl)imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency.
|
|
pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. ian_bell@merck.com
|
|
pubmed:publicationType |
Journal Article
|
