Microwave-Promoted Hetero-Diels-Alder Reactions of 2(1H)-Pyrazinones in Ionic Liquid Doped Solvents and on Solid Support
Poster Aug 21, 2006
Nadya Kaval, Erik Van der Eycken and C. Oliver Kappe
The readily available and broadly functionalized 2-azadiene system of the 2(1H)-pyrazinones easily undergo inter- and intramolecular Diels-Alder reactions with a wide range of dienophiles providing convenient routes to specifically substituted heterocycles.
The reactions in this series are known to be rather sluggish, requiring long reaction times, high temperatures and even sometimes high pressures. Since speed is generally recognized as an important factor in high-throughput synthesis, we have explored potential rate enhancements by controlled single-mode microwave irradiation (Emrys Synthesizer) in the presence of ionic liquids.
The results in solution phase were adapted to polystyrene supports using various acid labile linkers. This offers an efficient methodology for the separation of the resulting pyridines and pyridinones applying the concept of “traceless-linking”.
All steps in the solid-phase sequence were carried out under microwave irradiation. A detailed comparison between the microwave-assisted protocol and the conventional thermal method has been made for each reaction step.
Bioluminescent Kinase Profiling Systems For Characterizing Small Molecule Kinase InhibitorsPoster
In order to profile compounds against a broad panel of kinases, in-house profiling requires rigorous kinase assay development.READ MORE
Assessment of Oral LISPRO Treatment in Ameliorating Amyloid and Tau Pathology in Transgenic Alzheimer’s Mice ModelPoster
Ionic co-crystals of lithium salicylate with organic proline (LISPRO) showed better safety and pharmacokinetic profile of lithium in plasma and brain of wild-type and transgenic Alzheimer mice model compared to lithium salts.READ MORE
CiPA Phase 2 Study: validation of an automated microelectrode array (MEA) assay of hiPSC-derived cardiomyocyte electrophysiology for cardiac safety evaluationPoster
These results support the use of hSC-CM and MEA technology for preclinical assessment of proarrhythmic risk within the proposed CiPA paradigm, and, more generally, demonstrate that automation of the CM-MEA assay can achieve high reliability and throughput for cardiac risk assessment in vitro.READ MORE