REPUBLIC OF SERBIA

MINISTRY OF DEFENCE

www.mod.gov.rs

MINISTRY OF DEFENCE

Material Resources Sector

Defensive Technologies Department

Military Technical Institute

www.vti.mod.gov.rs

NOVEL 4-ARYL-4-OXO-N-PHENYL-2-AMINYLBUTYRAMIDES AS AChE REVERSIBLE INHIBITORS

maja vitorović-todorović

Military Technical Institute, Belgrade, majavitod@gmail.com

branko drakulić

Institute of Chemistry, Technology and Metallurgy, University of Belgrade, bdrakuli@chem.bg.ac.rs

sonja bauk

Military Technical Institute, Belgrade, bauk.sonja@gmail.com

LJUBA MANDIĆ

Faculty of Chemistry, University of Belgrade, ljmandic@chem.bg.ac.rs

Abstract: Widespread efforts to develop pharmacological pretreatments for the protection against nerve agent exposure emerged during the last decades. Such treatment should relieve the symptoms and decrease the mortality rate caused by nerve agent intoxications. One possible approach is the administration of cholinesterase reversible inhibitors in combination with the oxime and anticholinergic. Reversible inhibitors should protect acetylcholinesterase from covalent, irreversible inhibition by organophosphates. We synthesized twelve novel compounds based on 4-aryl-4-oxo-N-phenyl-2-aminylbutiramide structure, and tested their inhibition properties toward AChE. Five compounds showed reversible inhibition of AChE in low micromolar range. Structure-activity relationships were briefly discussed.

Key words: Acetylcholinesterase, nerve agents exposure, reversible inhibitors, prophylaxis.