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.

Autor: Bluke Z; a Riga Technical University , Riga , Latvia .; b Latvian Institute of Organic Synthesis , Riga , Latvia , and., Paass E; b Latvian Institute of Organic Synthesis , Riga , Latvia , and., Sladek M; c Merz Pharmaceuticals GmbH , Frankfurt am Main , Germany., Abel U; c Merz Pharmaceuticals GmbH , Frankfurt am Main , Germany., Kauss V; b Latvian Institute of Organic Synthesis , Riga , Latvia , and.
Jazyk: angličtina
Zdroj: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2016 Aug; Vol. 31 (4), pp. 664-73. Date of Electronic Publication: 2015 Jun 26.
DOI: 10.3109/14756366.2015.1057722
Abstrakt: 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 [(3)H]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 sp(3) CH2 is tolerated. This finding may pave the way for previously unexplored approaches for designing new ligands of the NMDA receptor.
Databáze: MEDLINE
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