(1) Department of Chemistry, ArQule Inc., 19 Presidential Way, Woburn, 01801 Massachusetts, US
Abstract:
A series of diverse indole-based chemotypes were synthesized from -tetrahydrocarboline (-THC) scaffolds prepared from commercially and readily available tryptamines and -ketoesters. Diversity can be generated within these chemotypes through the following strategies: (a) appendage of substituents to the -THC scaffold, prepared in situ or as a template, through further elaboration and (b) skeletal modifications to the -THC scaffold via ring forming or ring breaking reactions. The strategies described here are amenable to high throughput solution-phase parallel synthesis, providing access to novel indole-based screening libraries for drug discovery.Dedicated to Professor Spyros P. Perlepes