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

Journal of Enzyme Inhibition and Medicinal Chemistry 2016
Zanda Bluķe, Einars Paass, Meik Sladek, Ulrich Abel, Valerjans Kauss

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.

Keywords
3, 4-Dihydro-2H-1, 2-benzothiazine-3-carboxylic acid 1, 1-dioxide, glycine binding site, N-methyl-d-aspartate receptor, structure–activity relationship
DOI
10.3109/14756366.2015.1057722
Hyperlink
http://www.tandfonline.com/doi/full/10.3109/14756366.2015.1057722

Bluķe, Z., Paass, E., Sladek, M., Abel, U., Kauss, V. 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. Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, Vol.31, iss.4, pp.664-673. ISSN 1475-6366. e-ISSN 1475-6374. Available from: doi:10.3109/14756366.2015.1057722

Publication language
English (en)