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含氰基的不对称双吡啶鎓化合物的合成及其对塔崩和对氧磷抑制的乙酰胆碱酯酶的复活活性评估。

Synthesis of asymmetrical bispyridinium compounds bearing cyano-moiety and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase.

作者信息

Musilek Kamil, Holas Ondrej, Kuca Kamil, Jun Daniel, Dohnal Vlastimil, Dolezal Martin

机构信息

Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 50005 Hradec Kralove, Czech Republic.

出版信息

Bioorg Med Chem Lett. 2006 Nov 1;16(21):5673-6. doi: 10.1016/j.bmcl.2006.08.011. Epub 2006 Aug 24.

Abstract

Three asymmetrical AChE reactivators with cyano-moiety and propane linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by nerve agent tabun and insecticide paraoxon was tested in vitro and compared to pralidoxime, HI-6, obidoxime, K027, and K048. According to the results, three compounds seem to be promising against paraoxon-inhibited AChE. Better results were obtained for bisquaternary substances at least with one oxime group in position four. None of tested substances was able to satisfactorily reactivate tabun-inhibited AChE at concentration applicable for in vivo experiments.

摘要

通过对目前已知合成途径进行修饰,合成了三种具有氰基部分和丙烷连接基的不对称乙酰胆碱酯酶(AChE)重活化剂。在体外测试了它们对被神经毒剂塔崩和杀虫剂对氧磷抑制的AChE的重活化能力,并与解磷定、HI-6、双复磷、K027和K048进行了比较。根据结果,三种化合物似乎对被对氧磷抑制的AChE有前景。至少在4位有一个肟基的双季铵盐物质获得了更好的结果。在适用于体内实验的浓度下,没有一种测试物质能够令人满意地重活化被塔崩抑制的AChE。

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