Quinazolin-4-one alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists: structure-activity relationship of the C-2 side chain tether.

A series of 6-fluoro-3-(2-chlorophenyl)quinazolin-4-ones has been prepared, which contains a 2-fluorophenyl ring attached to C-2 by a variety of two-atom tethers. These compounds were used to probe the structure-activity relationship (SAR) for AMPA receptor inhibition. The relative potencies of the new compounds ranged from 11 nM to greater than 10 microM.

Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists.

Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated.

Characterization of the binding site for a novel class of noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonists.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is an ionotropic glutamate receptor that mediates fast excitatory synaptic transmission throughout the central nervous system. In addition to the glutamate binding site, allosteric modulatory sites on the receptor are inferred from the ability of synthetic compounds to affect channel function without interaction with the glutamate binding site. We have identified a novel class of potent, noncompetitive AMPA receptor antagonists typified by CP-465, 022 and CP-526,427.

Living on the edge: a phenomenological study of medically uninsured working Americans.

An estimated 35 to 50 million Americans have no medical insurance; the vast majority are employed persons and their dependents. This phenomenological study was developed to make visible the experience of working Americans living on the edge-forced to walk a fine line between health and illness without the safety net of medical insurance. A purposive sample of 12 individuals was asked, "What is it like to be working and without medical insurance? Based on textual analysis, using an adaptation of Colazzi's method, themes were grouped into four theme clusters: A Marginalized Life, Up Against Rocks and Hard Places, Making Choices-Chancing It, and Getting By-More or Less.

Methaqualone derivatives are potent noncompetitive AMPA receptor antagonists.

Quinazolin-4-one derivatives of methaqualone substituted at C-2 define a new class of noncompetitive antagonists at AMPA receptors.