Syntheses and spectroscopic characterization of some phosphoramidates as reversible inhibitors of human acetylcholinesterase and determination of their potency

The ability of phosphoramidates Me2NP(O)(Cl)(p-NHC6H4NO2) 1, Me2NP(O)(p-NHC6H4NO2)(2) 2, (CH3C6H4O-p)P(O)(p-NHC6H4NO2)(2) 3 and (CH3C6H4O-P)2P(O)(p-NHC6H4NO2) 4 to inhibit human acetylcholinesterase (hAChE) has been evaluated by a modified Ellman's method and spectrophotometric measurements. Results showed that compounds 1 and 2 do not have any inhibitory potency, whereas compounds 3 and 4 were reversible mixed inhibitors. The IC50 values for inhibitors 3 and 4 were 0.143 and 0.581 mM, respectively. The previously unknown compounds 3 and 4 were synthesized and characterized by H-1, C-13, P-31 NMR and IR spectroscopy and elemental analysis.