Design, synthesis and in vitro testing of 7-methoxytacrine-amantadine analogues: a novel cholinesterase inhibitors for the treatment of Alzheimer's disease

被引：29

作者：

Spilovska, Katarina ^{[1
,2
,3
]}

Korabecny, Jan ^{[1
,2
,3
,4
]}

Horova, Anna ^{[1
]}

Musilek, Kamil ^{[2
,5
]}

Nepovimova, Eugenie ^{[1
,2
]}

Drtinova, Lucie ^{[1
]}

Gazova, Zuzana ^{[5
]}

Siposova, Katarina ^{[5
]}

Dolezal, Rafael ^{[2
,4
]}

Jun, Daniel ^{[1
,2
]}

Kuca, Kamil ^{[2
,4
]}

机构：

[1] Univ Def, Fac Mil Hlth Sci, Dept Toxicol & Mil Pharm, Hradec Kralove 50001, Czech Republic

[2] Univ Hosp, Biomed Res Ctr, Hradec Kralove 50005, Czech Republic

[3] Natl Inst Mental Hlth, Klecany 25067, Czech Republic

[4] Univ Hradec Kralove, Fac Informat & Management, Ctr Basic & Appl Res, Hradec Kralove 50003, Czech Republic

[5] Slovak Acad Sci, Inst Expt Phys, Dept Biophys, Kosice 04001, Slovakia

来源：

MEDICINAL CHEMISTRY RESEARCH | 2015年 / 24卷 / 06期

关键词：

Alzheimer's disease; Inhibitor; Acetylcholinesterase; Butyrylcholinesterase; Amantadine; 7-MEOTA; NMDA RECEPTOR ANTAGONIST; ACETYLCHOLINESTERASE INHIBITORS; BIOLOGICAL EVALUATION; MEMANTINE; AMANTADINE; TACRINE; BUTYRYLCHOLINESTERASE; AGGREGATION; EXPRESSION; BLOCKADE;

D O I：

10.1007/s00044-015-1316-x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of cholinesterase inhibitors acting as dual binding site heterodimers for the management of Alzheimer's disease were developed. The series of 7-methoxytacrine (7-MEOTA)-amantadine ureas (11-17) was designed, prepared evaluated in vitro towards human acetyl/butyryl cholinesterase (hAChE, hBChE) and compared with the series of 7-MEOTA-amantadine thioureas (4-10). The heterodimers have different length of linkers combining 7-MEOTA and amantadine moieties. In comparison with 7-MEOTA, the newly synthesized compounds were better inhibitors of both cholinesterases. The urea analogues did not have the anticipated benefit of increased inhibitory activity and have comparable IC50 values with thiourea derivatives.

引用

页码：2645 / 2655

页数：11

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