Synthesis of 3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxides and their evaluation as ligands for NMDA receptor glycine binding site |
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Authors: | Zanda Bluke Einars Paass Meik Sladek Ulrich Abel |
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Affiliation: | 1. Riga Technical University, Riga, Latvia,;2. Latvian Institute of Organic Synthesis, Riga, Latvia, and;3. Latvian Institute of Organic Synthesis, Riga, Latvia, and;4. Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany |
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Abstract: | A series of 2-substituted 3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxides were synthesized and evaluated for their affinity to the glycine binding site of the N-methyl-d-aspartate (NMDA) receptor. The binding affinity was determined by the displacement of radioligand [3H]MDL-105,519 from rat cortical membrane preparations. The most attractive structures in the search for prospective NMDA receptor ligands were identified to be 2-arylcarbonylmethyl substituted 3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxides. It has been demonstrated for the first time that the replacement of NH group in the ligand by sp3 CH2 is tolerated. This finding may pave the way for previously unexplored approaches for designing new ligands of the NMDA receptor. |
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Keywords: | 3 4-Dihydro-2H-1 2-benzothiazine-3-carboxylic acid 1 1-dioxide glycine binding site N-methyl- smallcaps smallerCapital" >d-aspartate receptor structure–activity relationship |
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