Microwave Assisted Synthesis of Substituted 2(1H)-Quinolones as Maxi-K+ Channel Openers
Poster Apr 01, 2006
Toma Glasnov, Wolfgang Stadlbauer and C. Oliver Kappe
Here we present a novel synthetic strategy for synthesis of 4-aryl-2(1H)-quinolone lead compounds for the treatment of male ED. The MW-reaction protocols are high-diversity generating, flexible, amenable to high-speed MAOS, scalable and involve commercially available building blocks. Our approach for making the 4-arylquinolones includes a cyclization step, chlorination/hydrolysis, Suzuki C-C coupling, bromination, and finally a Heck reaction, all under microwave conditions.
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