Linked Life Data

8027985

Source:http://linkedlifedata.com/resource/pubmed/id/8027985

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1994-8-9
pubmed:abstractText
A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60v-src tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity. While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60v-src kinases, but several compounds did show some specificity (> 20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60v-src, while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC50S in the range 2-25 microM, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2033-42
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8027985-3T3 Cells, pubmed-meshheading:8027985-Animals, pubmed-meshheading:8027985-Blotting, Western, pubmed-meshheading:8027985-Cells, Cultured, pubmed-meshheading:8027985-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:8027985-Fibroblast Growth Factor 2, pubmed-meshheading:8027985-Humans, pubmed-meshheading:8027985-Indoles, pubmed-meshheading:8027985-Magnetic Resonance Spectroscopy, pubmed-meshheading:8027985-Mice, pubmed-meshheading:8027985-Oncogene Protein pp60(v-src), pubmed-meshheading:8027985-Oxidation-Reduction, pubmed-meshheading:8027985-Phosphorylation, pubmed-meshheading:8027985-Protein-Tyrosine Kinases, pubmed-meshheading:8027985-Receptor, Epidermal Growth Factor, pubmed-meshheading:8027985-Structure-Activity Relationship, pubmed-meshheading:8027985-Tumor Cells, Cultured
pubmed:year
1994
pubmed:articleTitle
Tyrosine kinase inhibitors. 3. Structure-activity relationships for inhibition of protein tyrosine kinases by nuclear-substituted derivatives of 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide).
pubmed:affiliation
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't