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4995
Design and Synthesis of Novel Quinoxaline-2,3-dione AMPA/GlyN Receptor Antagonists: Amino Acid Derivatives
Design and Synthesis of Novel Quinoxaline-2,3-dione AMPA/GlyN Receptor Antagonists: Amino Acid Derivatives
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Sham S. Nikam,*† John J. Cordon,‡ Daniel F. Ortwine,† Tycho H. Heimbach,§ Anthony C. Blackburn,§ Mar
1999
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PNQX (1,4,7,8,9,10-hexahydro-9-methyl-6-nitropyrido[3,4-f]quinoxaline-2,3-dione) is a potent AMPA (IC50 = 0.063 μM) and GlyN (IC50 = 0.37 μM) receptor antagonist that was developed in our laboratories. While possessing a desirable in vitro and in vivo activity profile, this compound suffers from low aqueous solubility. In an effort to improve its potency and physical properties, we have designed and synthesized novel ring-opened analogues 4, 6, 9, and 11. Modeling analyses demonstrated that, w...
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