The discovery of potent cRaf1 kinase inhibitors

Authors
Lackey, K Cory, M Davis, R Frye, SV Harris, PA Hunter, RN Jung, DK McDonald, OB McNutt, RW Peel, MR Rutkowske, RD Veal, JM Wood, ER
Citation
K. Lackey et al., The discovery of potent cRaf1 kinase inhibitors, BIOORG MED, 10(3), 2000, pp. 223-226
Citations number
17
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
3
Year of publication
2000
Pages
223 - 226
Database
ISI
SICI code
0960-894X(20000207)10:3<223:TDOPCK>2.0.ZU;2-2
Abstract
A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesiz ed and evaluated as cRaf-1 kinase inhibitors. The key features of the molec ules were the donor/acceptor motif common to kinase inhibitors and a critic al acidic phenol flanked by two substitutions. Diverse 5-position substitut ions provided compounds with low nanomolar kinase enzyme inhibition and inh ibited the intracellular MAPK pathway. (C) 2000 Elsevier Science Ltd. All r ights reserved.