Article
Syntheses of Substituted 4-(Indol-3-yl)quinazolines, a New Class of EGFR-Tyrosinkinase Inhibitors
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Published: | March 20, 2006 |
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Earlier investigations with inhibitors of the epidermal growth factor receptor (EGFR) family of tyrosine kinases led to the highly active 4-anilinoquinazolines Gefitinib (1) (Iressa®; Astra Zeneca) and Erlotinib (2) (Tarceva®; Genentech/OSI Pharmaceuticals/Roche).
We present the syntheses of the compounds (3), (4) and (5) in which the 4-anilino-moiety is exchanged by a substituted indol-3-yl heterocycle. Compounds (3), (4) and (5) represents a more fundamental change in the pharmacophore and claim an excellent EGFR-tyrosine kinase inhibition activity.
A detailed discussion of the synthetic results will be presented together with NMR-spectral, x-ray and pharmacologicalresults.
Figure 1 [Fig. 1].