Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
Bioorg Chem. 2018 Oct;80:668-673. doi: 10.1016/j.bioorg.2018.07.017. Epub 2018 Jul 17.
Based on the presence of carbamate moiety, twenty salicylanilide N-monosubstituted carbamates concomitantly with their parent salicylanilides and five newly prepared 4-chlorophenyl carbamates obtained from isocyanates were investigated using Ellman's method for their in vitro inhibitory activity against acetylcholinesterase (AChE) from electric eel and butyrylcholinesterase (BChE) from equine serum. The carbamates and salicylanilides exhibited mostly a moderate inhibition of both cholinesterase enzymes with IC values ranging from 5 to 235 µM. IC values for AChE were in a narrower concentration range when compared to BChE, but many of the compounds produced a balanced inhibition of both cholinesterases. The derivatives were comparable or superior to rivastigmine for AChE inhibition, but only a few of carbamates also for BChE. Several structure-activity relationships were identified, e.g., N-phenethylcarbamates produce clearly favourable BChE inhibition. The compounds also share convenient physicochemical properties for CNS penetration.
基于氨基甲酸酯部分的存在，二十种水杨酰苯胺 N-单取代氨基甲酸酯与它们的母体水杨酰苯胺以及从异氰酸酯获得的五个新制备的 4-氯苯基氨基甲酸酯一起，使用 Ellman 法，对来自电鳗的乙酰胆碱酯酶（AChE）和马血清中的丁酰胆碱酯酶（BChE）进行了体外抑制活性的研究。氨基甲酸酯和水杨酰苯胺对两种胆碱酯酶都表现出中等程度的抑制，IC 值范围为 5 至 235µM。与 BChE 相比，AChE 的 IC 值范围较窄，但许多化合物对两种胆碱酯酶都产生了平衡的抑制作用。这些衍生物在抑制 AChE 方面与利伐斯的明相当或更优，但只有少数氨基甲酸酯对 BChE 也有抑制作用。确定了几种构效关系，例如，N-苯乙基氨基甲酸酯对 BChE 产生明显有利的抑制作用。这些化合物还具有便于 CNS 穿透的便利理化性质。
