与用于治疗阿尔茨海默病的药物利伐斯的明相关的苯基氨基甲酸酯的合成及胆碱酯酶活性

Synthesis and cholinesterase activity of phenylcarbamates related to Rivastigmine, a therapeutic agent for Alzheimer's disease.

作者信息

Mustazza Carlo, Borioni Anna, Del Giudice Maria Rosaria, Gatta Franco, Ferretti Rosella, Meneguz Annarita, Volpe Maria Teresa, Lorenzini Paola

机构信息

Laboratorio di Chimica del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.

出版信息

Eur J Med Chem. 2002 Feb;37(2):91-109. doi: 10.1016/s0223-5234(01)01324-1.

DOI:10.1016/s0223-5234(01)01324-1

PMID:11858843

Abstract

In order to develop new cholinesterase agents effective against Alzheimer's disease (AD) we synthesized some phenylcarbamates structurally related to Rivastigmine and evaluated their in vitro and in vivo biological activity. Among the compounds which displayed the most significant in vitro activity, 1-[1-(3-dimethylcarbamoyloxyphenyl)ethyl]piperidine (31b), in addition to a simple and cheaper synthesis, showed lower toxicity and very similar therapeutic index in comparison with Rivastigmine.

摘要

为了开发对阿尔茨海默病（AD）有效的新型胆碱酯酶药物，我们合成了一些结构上与卡巴拉汀相关的苯基氨基甲酸酯，并评估了它们的体外和体内生物活性。在显示出最显著体外活性的化合物中，1-[1-(3-二甲基氨基甲酰氧基苯基)乙基]哌啶（31b）除了合成简单且成本较低外，与卡巴拉汀相比还显示出较低的毒性和非常相似的治疗指数。