Strategies for the synthesis of novel indole alkaloid-based screening libraries for drug discovery.
A series of diverse indole-based chemotypes were synthesized from beta-tetrahydrocarboline (beta-THC) scaffolds prepared from commercially and readily available tryptamines and alpha-ketoesters. Diversity can be generated within these chemotypes through the following strategies: (a) appendage of substituents to the beta-THC scaffold, prepared in situ or as a template, through further elaboration and (b) skeletal modifications to the beta-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.
Fokas
Demosthenes
D
Department of Chemistry, ArQule Inc., 19 Presidential Way, Woburn, Massachusetts 01801, USA. dfokas@arqule.com
Yu
Libing
L
Baldino
Carmen M
CM
D002243:Carbolines / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure
D002243:Carbolines; D007202:Indicators and Reagents; D026121:Indole Alkaloids