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 CH 2 is tolerated. This finding may pave the way for previously unexplored approaches for designing new ligands of the NMDA receptor.

Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs

“…The PMB-protected hybrid 24 was deprotected using trifluoroacetic acid 35 to furnish δ-sultam 33 in fair yield (53%, Scheme 6).…”