Epilepsy and other seizure disorders are not adequately managed with currently available drugs. We recently synthesized a series of dibromophenyl enaminones and demonstrated that AK6 and E249 were equipotent to previous analogs but more efficacious in suppressing neuronal excitation. Here we examined the actions of these lead compounds on in vitro and in vivo seizure models. In vitro seizures w...

Condensation of phthalimidoacetone (1) with DMFDMA (N,N-Dimethylformamide dimethyl acetal) has afforded enaminone 2. Refluxing 2 with equimolecular amounts of benzaldehyde and urea in acetic acid afforded a mixture of tetrahydropyrimidine 5 and the dihydropyridine 6. Compound 2 undergoes self-condensation on heating in acetic acid or under microwave irradiation in presence of acidic zeolite to ...

We report one-pot and chemoselective Knoevenagel-type reactions using highly stable amides and lactams as the electrophilic substrates. The method is based on the in situ activation of amide carbonyl with triflic anhydride and a subsequent reaction with carbanions generated in situ from carbonyl compounds. The amide-based method is an alternative to the versatile thioamide-based Eschenmoser sul...

We have studied the role of Cu(+)-phenantroline as a catalyst in the cyclization of N-aryl-enaminones using density-functional theory computations. The catalyst was found to bind the substrate upon deprotonation of its eneaminone, and to dramatically increase the acidity of the carbon adjacent to the ketone functionality. The deprotonation of this carbon atom yields a carbanion which attacks th...