Synthesis, Spectroscopic Characterization and Structure-Activity Relationship of Some Phosphoramidothioate Pesticides

In this work, some phosphoramidothioates (PATs) with the general formula of (CH3O)2P(S)X and (CH3O)(CH3S)P(O)X, where, X = NH2 (1 & 6), NH(CH3) (2 & 7), N(CH3)2 (3 & 8), N(Et)2 (4 & 9), (CH3CH2O)2P(S)NH(CH3) (5) and (CH3CH2O)(CH3CH2S)P(O)NH(CH3) (10), were synthesized and characterized by 31P, 31P{1H}, 13C and 1H NMR spectroscopy. The ability of the compounds to inhibit AChE was predicted by PASS software (version 1.193). They were also experimentally evaluated by a modified Ellman's assay. The structure-activity relationship (SAR) between IC50and some physico-chemical properties such as lipophilicity (logP), electronic and steric effects of the compounds was studied. The logP values were experimentally determined by the shake-flask (gas chromatography) method. Inhibitory potency for the compounds 1-10 was 1 (3.38 mM) > 2 (3.97 mM) > 3 (4.75 mM) > 4 (6.00 mM) > 5 (5.51 mM) > 6 (0.07 mM) > 7 (0.23 mM) > 8 (0.39 mM) > and 9 (0.55 mM) > 10 (0.51 mM), respectively. IC50 and logP parameters of the P=O moiety were more than the P=S moiety in PAT analogues.