title: 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.
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 [(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.
authors.affiliation: a Riga Technical University , Riga , Latvia .|b Latvian Institute of Organic Synthesis , Riga , Latvia , and.
authors.forename: Zanda
authors.initials: Z
authors.lastname: Bluke
authors.affiliation: b Latvian Institute of Organic Synthesis , Riga , Latvia , and.
authors.forename: Einars
authors.initials: E
authors.lastname: Paass
authors.affiliation: c Merz Pharmaceuticals GmbH , Frankfurt am Main , Germany.
authors.forename: Meik
authors.initials: M
authors.lastname: Sladek
authors.affiliation: c Merz Pharmaceuticals GmbH , Frankfurt am Main , Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Abel
authors.affiliation: b Latvian Institute of Organic Synthesis , Riga , Latvia , and.
authors.forename: Valerjans
authors.initials: V
authors.lastname: Kauss
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C000614207:3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxide; D048588:Benzoxazines; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine
keywords: 1-dioxide; 2-benzothiazine-3-carboxylic acid 1; 3; 4-Dihydro-2H-1; N-methyl-d-aspartate receptor; glycine binding site; structure–activity relationship