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

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• 作者：Katarina Spilovska ; Jan Korabecny ; Anna Horova…
• 关键词：Alzheimer’s disease ; Inhibitor ; Acetylcholinesterase ; Butyrylcholinesterase ; Amantadine ; 7 ; MEOTA
• 刊名：Medicinal Chemistry Research
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：24
• 期：6
• 页码：2645-2655
• 全文大小：850 KB
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• 作者单位：Katarina Spilovska (1) (2) (6)
  Jan Korabecny (1) (2) (3) (6)
  Anna Horova (1)
  Kamil Musilek (2) (5)
  Eugenie Nepovimova (1) (2)
  Lucie Drtinova (1)
  Zuzana Gazova (5)
  Katarina Siposova (5)
  Rafael Dolezal (2) (3)
  Daniel Jun (1) (2)
  Kamil Kuca (2) (3)
  
  1. Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic
  2. Biomedical Research Centre, University Hospital, Sokolska 581, 500 05, Hradec Kralove, Czech Republic
  6. National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic
  3. Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic
  5. Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01, Kosice, Slovak Republic
  
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Cell Biology;
• 出版者：Springer US
• ISSN：1554-8120

文摘

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-strong class="EmphasisTypeBold">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-strong class="EmphasisTypeBold">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.