67342-12-5Relevant articles and documents
Synthesis and biological activity of N,N-dialkylaminoalkyl-substituted bisindolyl and diphenyl pyrazolone derivatives
Brana, Miguel F.,Gradillas, Ana,Ovalles, Angel G.,Lopez, Berta,Acero, Nuria,Llinares, Francisco,Mingarro, Dolores Munoz
, p. 9 - 16 (2007/10/03)
New compounds, structurally related to the potent protein kinase C inhibitor staurosporine, with a bisindolylpyrazolone framework and substituted on the pyrazolone nitrogens with N,N-dialkylaminoalkyl side chain, were synthesized and evaluated for growth-
A new photocyclization approach to the rare 1,3-thiazino[6,5-b]indol-4-one derivatives
Kutschy, Peter,Suchy, Mojmír,Andreani, Aldo,Dzurilla, Milan,Rossi, Maddalena
, p. 9281 - 9283 (2007/10/03)
The analogs of indole phytoalexin cyclobrassinon have been prepared in four steps from corresponding 1-substituted 2-chloroindole-3-carboxylic acids, employing a hitherto unknown photochemical cyclization of new indolyl thiocarbamates to 1,3-thiazino[6,5-b]indole-4-one derivatives as a key step.
Tyrosine kinase inhibitors. 4. Structure-activity relationships among N- and 3-substituted 2,2'-dithiobis(1H-indoles) for in vitro inhibition of receptor and nonreceptor protein tyrosine kinases
Palmer,Rewcastle,Thompson,Boyd,Showalter,Sercel,Fry,Kraker,Denny
, p. 58 - 67 (2007/10/02)
A series of 3-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC50s 1-20 μM), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N- thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC50s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol- containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.
