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In the early stages of the war, when Grafton’s regiment was ordered into western Virginia, where the fighting was heaviest, Grant personally went to Boston to pick up this detachment at its starting point in New York city. 8, 1818, gpsproversion110815forviamichelinx950 15ÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃÃöÃÃÃÃæÃôÃÃÃæÃÃÃà Ã. How will you do it?.A new family of quinolinic acid inhibitors. Synthesis and biological activity. A new class of glutamate antagonists has been developed based on our previous work demonstrating that quinolinic acid (QUIN) is neurotoxic and that 2-methyl-QUIN (2-MeQUIN) is not. In the present study, we have synthesized a series of 2,4-disubstituted quinolinic acids and attempted to elucidate the structure-activity relationship (SAR) in order to determine the structural features required for neurotoxicity and to determine which of the amino acid conformation available to the drug is critical in determining activity. New derivatives were evaluated in vitro for neurotoxicity, platelet activation, and excitotoxicity. Four compounds were found to be neurotoxic, as evidenced by their ability to reduce the mitochondrial membrane potential (MMP) in cultured hippocampal neurons. The most potent of these compounds was 2,4-diethyl-3-methoxy-quinolinic acid (2,4-DEO-3-MeQUIN). Among the nonneurotoxic compounds, the one with the greatest inhibitory effect on platelet aggregation in vitro was also the most active in reducing quinolinic acid-induced excitotoxicity. Although the position of the amino acid side chain on the quinolinic acid molecule is not critical for neurotoxicity, replacement of the ethyl side chain in 2-MeQUIN with a methyl group increased the inhibition of platelet aggregation and excitotoxicity. This 37a470d65a
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