OBJECTIVES We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus. MATERIALS AND METHODS Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg(2+) model. RESULTS Low concentrati...

An efficient synthesis of 2H-thiopyran-3,4-dicarboxylate derivatives via one-pot reactions between acetylenic esters, arylisothiocyanates and enaminones in water is described.The advantages of this work were: (1) the reaction was performed under neutral and more important in water as the solvent. (2) No catalyst was required for this reaction. (3) The simplicity of the present procedure made it...

The first total synthesis of the marine macrolide miyakolide has been achieved, and its absolute stereochemistry has been determined. The carbon skeleton is assembled in a convergent fashion from three fragments via esterification, [3 + 2] dipolar cycloaddition, and aldol addition. The utility of â-ketoimide aldol reactions in fragment coupling was demonstrated on fully elaborated intermediates...

The first example of the use of an N-heterocyclic carbene (NHC) as an organocatalyst for the activation of isocyanides was demonstrated. On the basis of previous reports on the interaction between NHCs and isocyanides, we developed a catalytic cycle involving transient imidoyl intermediate. The reaction of ketones with isocyanides produced the corresponding enaminones with high efficiency. Cont...

GABAA receptor (R) positive allosteric modulators that selectively modulate GABAARs containing 2and/or 3over 1subunits have been reported across diverse chemotypes. Examples include loreclezole, mefenamic acid, tracazolate, and etifoxine. In general,“ 2/3-selective” GABAAR positive allosteric modulators are nonbenzodiazepines (nonBZs), do not show -subunit isoform selectivity, yet have anxiolyt...