SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW ACETYLCHOLINESTERASE INHIBITORS - MORPHOLINOALKYLCARBAMOYLOXYESEROLINE DERIVATIVES
SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW ACETYLCHOLINESTERASE INHIBITORS - MORPHOLINOALKYLCARBAMOYLOXYESEROLINE DERIVATIVES
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DOI：
10.1016/0960-894x(95)00371-y
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发表时间：
1995-09-21
影响因子：
2.7
通讯作者：
PAGELLA, P
中科院分区：
文献类型：
--
作者：
ALISI, MA;BRUFANI, M;PAGELLA, P
几种新的有效的乙酰胆碱酯酶抑制剂已被合成为治疗阿尔茨海默病的潜在药物。毒扁豆碱(MF201)是毒扁豆碱的一种药物类似物，正在进行临床评价。为了得到新的毒扁豆碱类似物，用不同链长(C2-C12)的omega-吗啉烷基氨基甲酰氧基取代了甲基氨基甲酰氧基。当链长由八到十二个亚甲基组成时，体外抑制作用很强。C10和C11的抑制活性是庚基毒扁豆碱的7倍。
Several new potent acetylcholinesterase inhibitors have been synthesised as potential drugs for the treatment of Alzheimer's disease. Heptylphysostigmine (MF201) is a drug analogue of physostigmine under clinical evaluation. In order to obtain new physostigmine analogues, the methylcarbamoyloxy group was substituted with omega-morpholinoalkylcarbamoyloxy moieties of different chain lengths (C2-C12). Potent in vitro inhibition is seen when the chain length is composed of eight to twelve methylene groups. The inhibitory activity of the C10 and C11 is 7-fold greater with respect to heptylphysostigmine.