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rdf:type |
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lifeskim:mentions |
umls-concept:C0050423,
umls-concept:C0138837,
umls-concept:C0205531,
umls-concept:C0226896,
umls-concept:C0243077,
umls-concept:C0441655,
umls-concept:C0442027,
umls-concept:C0935763,
umls-concept:C1515655,
umls-concept:C1527415,
umls-concept:C2349975
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pubmed:issue |
10
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pubmed:dateCreated |
1998-5-28
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pubmed:abstractText |
We previously reported compound 1 as a potent farnesyl protein transferase (FPT) inhibitor that exhibited reasonable pharmacokinetic stability and showed moderate in vivo activity against a variety of tumor cell lines. The analogous C-11 single compound, pyridylacetamide 2, was found to be more potent than 1 in FPT inhibition. Further studies showed that modification of the ethano bridge of the tricyclic ring system by conversion into a double bond with concomitant introduction of a single bond at C-11 piperidine resulted in compound 3 that had superior FPT activity and pharmacokinetic stability. Compound 4, a 5-bromo-substituted analogue of 3, showed improved FPT activity, had good cellular activity, and demonstrated a remarkably improved pharmacokinetic profile with AUC of 84.9 and t1/2 of 82 min. Compound4 inhibited the growth of solid tumor in DLD-1 model by 70% at 50 mpk and 52% at 10 mpk.
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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 |
0022-2623
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pubmed:author |
pubmed-author:BishopW RWR,
pubmed-author:BryantM SMS,
pubmed-author:DollR JRJ,
pubmed-author:GangulyA KAK,
pubmed-author:GirijavallabhanVV,
pubmed-author:LinDD,
pubmed-author:LiuJJ,
pubmed-author:NjorogeF GFG,
pubmed-author:NomeirA AAA,
pubmed-author:PinteFF,
pubmed-author:VibulbhanBB
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1561-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9572881-Administration, Oral,
pubmed-meshheading:9572881-Alkyl and Aryl Transferases,
pubmed-meshheading:9572881-Animals,
pubmed-meshheading:9572881-Antineoplastic Agents,
pubmed-meshheading:9572881-Biological Availability,
pubmed-meshheading:9572881-Cyclic N-Oxides,
pubmed-meshheading:9572881-Drug Screening Assays, Antitumor,
pubmed-meshheading:9572881-Enzyme Inhibitors,
pubmed-meshheading:9572881-Female,
pubmed-meshheading:9572881-Humans,
pubmed-meshheading:9572881-Mice,
pubmed-meshheading:9572881-Mice, Nude,
pubmed-meshheading:9572881-Neoplasm Transplantation,
pubmed-meshheading:9572881-Oncogene Protein p21(ras),
pubmed-meshheading:9572881-Pyridines,
pubmed-meshheading:9572881-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
Potent, selective, and orally bioavailable tricyclic pyridyl acetamide N-oxide inhibitors of farnesyl protein transferase with enhanced in vivo antitumor activity.
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pubmed:affiliation |
Schering-Plough Research Institute, Departments of Chemistry and Tumor Biology, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
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pubmed:publicationType |
Journal Article
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