Korte W D, Shih M L
U.S. Army Medical Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
J Pharm Sci. 1993 Aug;82(8):782-6. doi: 10.1002/jps.2600820805.
The principal initial degradation products of two bis(pyridinium)aldoxime organophosphate-inhibited acetylcholinesterase reactivators, 1 (HI-6) and 3 (HS-6), in concentrated nonbuffered aqueous solutions approximating potential therapeutic dosage concentrations were found to be the carboxylic acid derivatives 2 and 4 formed from the hydrolysis of the amide functional group. Compounds 2 and 4 were prepared by heating 1 and 3 in the presence of high concentrations of hydroxylamine hydrochloride and characterized by 1H and 13C NMR, IR, and UV analyses. Estimates of the rates of hydrolysis of the amide groups in 1 and 3 and in model compounds 5, 7, and 8 under similar conditions were determined. The unexpectedly rapid hydrolysis of the amide groups in 1 and 3 was attributed to both the hydrogen ion catalysis of the concentrated aqueous solutions of the unusually acidic bis(pyridinium)aldoximes 1 and 3 and general acid catalysis by the aldoxime group.
在接近潜在治疗剂量浓度的浓缩非缓冲水溶液中，两种双（吡啶鎓）醛肟有机磷酸酯抑制的乙酰胆碱酯酶复活剂1（HI-6）和3（HS-6）的主要初始降解产物被发现是由酰胺官能团水解形成的羧酸衍生物2和4。化合物2和4通过在高浓度盐酸羟胺存在下加热1和3制备，并通过1H和13C NMR、IR和UV分析进行表征。测定了在类似条件下1和3以及模型化合物5、7和8中酰胺基团的水解速率估计值。1和3中酰胺基团出乎意料的快速水解归因于异常酸性的双（吡啶鎓）醛肟1和3的浓水溶液的氢离子催化以及醛肟基团的一般酸催化。
