Langenberg J P, De Jong L P, Otto M F, Benschop H P
Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.
Arch Toxicol. 1988;62(4):305-10. doi: 10.1007/BF00332492.
Methamidophos (CH3O(NH2)P(O)SCH3) and phosphoramidates, with the general structure RO(NH2)P(O)OC6H4-p-NO2, in which R = C2H5, C1CH2CH2, FCH2CH2 and F3CCH2, as well as (NH2)2P(O)OC6H4-p-NO2 were synthesized to investigate the relationship between the rates of inhibition and of spontaneous reactivation of AChE inhibited by these organophosphates and their potential as prophylactics against nerve agent poisoning. The phosphoramidates inhibit electric eel acetylcholinesterase (EEAChE), the bimolecular inhibition rate constants ranging from 5 x 10(4) to 3 x 10(6) M-1.min-1 at pH 7.5, 25 degrees C. The inhibited enzymes reactivate spontaneously, with half-lives ranging from 1.3 to 15 h at pH 7.5, 25 degrees C. These half-lives increase 2-4 fold when the temperature is raised to 37 degrees C. Reactivation is accelerated by micromolar concentrations of oximes such as obidoxime and HI-6. Aging of the inhibited enzymes was not observed. Nevertheless, reactivation appears to be incomplete for some of the inhibited enzymes. The title compounds seem promising as prophylactic agents against nerve agent intoxication.
合成了甲胺磷（CH3O(NH2)P(O)SCH3）和具有通式RO(NH2)P(O)OC6H4-p-NO2的氨基磷酸酯（其中R = C2H5、C1CH2CH2、FCH2CH2和F3CCH2）以及(NH2)2P(O)OC6H4-p-NO2，以研究这些有机磷酸酯对乙酰胆碱酯酶（AChE）的抑制速率和自发重活化速率之间的关系，以及它们作为预防神经毒剂中毒药物的潜力。氨基磷酸酯可抑制电鳗乙酰胆碱酯酶（EEAChE），在pH 7.5、25℃条件下，双分子抑制速率常数范围为5×10(4)至3×10(6) M-1·min-1。被抑制的酶会自发重活化，在pH 7.5、25℃条件下，半衰期范围为1.3至15小时。当温度升至37℃时，这些半衰期会增加2至4倍。微摩尔浓度的肟（如双复磷和HI-6）可加速重活化。未观察到被抑制酶的老化现象。然而，对于某些被抑制的酶，重活化似乎并不完全。这些标题化合物作为预防神经毒剂中毒的药物似乎很有前景。
