Structure-Activity Relationship in Phosphoramidates

In this research, by using the PASS Software, probability anti-acetylcholinesterase propertiec of two hundred and twenty-five phosphoramide molecules was predicted and then of among them of ten molecules with highest probability anti-acetylcholinesterase with general formula: [NH(CH3)]P(O)[SCH3][OCH3] (44), [N(CH3)2]P(S)[OCH3)[OCH3] (46), [NH(CH3)]P(O)[SCH2CH3] [OCH2CH3] (47), [N(CH3)2]P(O)[CN]2 (93),[2,4,5-Cl3-C6H2O]P(O)[OCH3][N(CH3)2] (99), [2,4,5-Cl3-C6H2O]P(O)[OCH2CH3][N(CH3)2] (103), [p-Cl-C6H4O]2P(O)[N(CH3)2] (178), [p-CH3-C6H4O]2P(O) [N(CH3)2] (179), [C6H5O]2P(O)[N(CH3)](183), [p-CH3C6H4O]P(O)[F][N(CH3)2] (217) was selected. After synthesis, purification and characterization of target compounds was performed by using the technique of IR, GC-Mass, X-Ray and 1H, 13C, 19F, 31P NMR spectroscopy. The lipophilicity parameter and the inhibitory potential for the target compounds was determined by the shake flask and the Ellman method respectively. The structure-activity relationships of the target compounds show that the log P parameter has more correlation with IC50 than the electronic and the stric parameters.