1,2,4-Thiadiazole derivatives as effective NMDA receptor blockers with anticholinesterase activity and antioxidant properties

Abstract

New 5-anilino-1,2,4-thiadiazole derivatives with different substituents at position 3 were synthesized and their influence on the key binding sites of NMDA receptors, inhibitory activity against acetylcholinesterase, butyrylcholinesterase, and carboxylesterase, as well as antioxidant properties were studied. The compounds with a 2-aminopropyl fragment were found to be efficient blockers of allosteric modulator [³H]ifenprodil binding site of the NR2B-containing NMDA receptors and moderate butyrylcholinesterase inhibitors. Some compounds were found to be able to simultaneously block the [³H]ifenprodil and intrachannel [³H]MК-801 binding sites of NMDA receptors. Compounds containing a 2-aminopropenyl fragment did not exhibit activity against NMDA receptors and butyrylcholinesterase, but showed high radical-scavenging activity.