磷酰胺酸酯作为乙酰胆碱酯酶抑制剂的构效关系研究。

Structure-activity study of phosphoramido acid esters as acetylcholinesterase inhibitors.

作者信息

Ghadimi Saied, Valmoozi Ali Asghar Ebrahimi, Pourayoubi Mehrdad, Samani Keyvan Asad

机构信息

Department of Chemistry, Imam Hossein University, Tehran, Iran.

出版信息

J Enzyme Inhib Med Chem. 2008 Aug;23(4):556-61. doi: 10.1080/14756360701731981.

DOI:10.1080/14756360701731981

PMID:18666002

Abstract

Phosphoramido acid esters (CH(3))(2)NP(O)X(p-OC(6)H(4)-CH(3)) (containing P-Cl (1), P-O (2), P-F (3), P-CN (5), and P-N (4,6) bonds, X for 2, 4 and 6 is OCH(3), (C(2)H(5))(2)N and morpholin) have been synthesized to investigate the structure-activity study of AChE enzyme inhibition, through the parameters logP, delta(31)P and IC(50). After their characterization by (31)P, (31)P{(1)H}, (13)C, (1)H NMR, IR and mass spectroscopy, the parameters logP and delta(31)P ((31)P chemical shift in NMR) were used to evaluated the lipophilicity and electronical properties. The ability of compounds to inhibit human AChE was predicted by PASS software (version 1.193), and experimentally evaluated by a modified Ellman's assay.

摘要

合成了磷酰胺酸酯(CH(3))(2)NP(O)X(p-OC(6)H(4)-CH(3))（含有P-Cl (1)、P-O (2)、P-F (3)、P-CN (5)和P-N (4,6)键，2、4和6的X分别为OCH(3)、(C(2)H(5))(2)N和吗啉），通过logP、δ(31)P和IC(50)参数研究乙酰胆碱酯酶（AChE）抑制的构效关系。通过(31)P、(31)P{(1)H}、(13)C、(1)H核磁共振、红外光谱和质谱对其进行表征后，利用logP和δ(31)P（核磁共振中的(31)P化学位移）参数评估亲脂性和电子性质。通过PASS软件（版本1.193）预测化合物抑制人AChE的能力，并通过改良的Ellman检测法进行实验评估。