Marta M, Castellano C, Oliverio A, Pavone F, Pagella P G, Brufani M, Pomponi M
Istituto di Chimica, Università Cattolica S.C. Facoltà di Medicina A. Gemelli, Rome, Italy.
Life Sci. 1988;43(23):1921-8. doi: 10.1016/s0024-3205(88)80010-9.
The synthesis of a series of physostigmine analogs, in which the methylcarbamyl group has been substituted with monoalkylcarbamyl, dimethyl- and diethylcarbamyl groups, is reported. These compounds were prepared with the aim of investigating their possible therapeutic effects in the treatment of Alzheimer's type dementia. The new analogs of physostigmine are inhibitors of acetylcholinesterase from Electroforus electricus, with a value of the reactivation constant, k3 smaller than the one of physostigmine. The percentage of anticholinesterase activity in vitro and in vivo, the acute toxicity and some behavioural effects were also evaluated for selected derivatives. The reactivation constant, in vitro, supports the view that the derivatives described would be more suitable for therapeutic use than physostigmine.
据报道，合成了一系列毒扁豆碱类似物，其中甲基氨基甲酰基已被单烷基氨基甲酰基、二甲基和二乙基氨基甲酰基取代。制备这些化合物的目的是研究它们在治疗阿尔茨海默型痴呆症方面可能的治疗效果。毒扁豆碱的新类似物是电鳐乙酰胆碱酯酶的抑制剂，其复活常数k3的值小于毒扁豆碱的k3值。还对选定的衍生物评估了体外和体内抗胆碱酯酶活性的百分比、急性毒性和一些行为影响。体外复活常数支持这样一种观点，即所描述的衍生物比毒扁豆碱更适合用于治疗。
