Homodimeric tacrine congeners as acetylcholinesterase inhibitors

Ming Kuan Hu, Li Ju Wu, George Hsiao, Mao Hsiung Yen

研究成果: 雜誌貢獻文章同行評審

111 引文 斯高帕斯(Scopus)

摘要

In the search for highly selective and potent derivatives of tacrine (1a), a number of homodimeric tacrine congeners were synthesized and conducted for their effects on rat acetylcholinesterase (ACHE) and human butyrylcholinesterase (BChE) inhibitions. Heptylene-linked bis-(6-chloro)-tacrine (3h) was found up to 3000- and 3-fold more potent in inhibiting rat AChE than tacrine and the unsubstituted bis-tacrine 3b, respectively. Changes in the size of the carbocyclic ring of the dimeric tacrine reduced both the selectivity and the potency of AChE inhibition as compared to 3b. Inserting an aza into the tacrine nucleus as the desired isosteres 3j-m resulted in moderate potency but tended to be detrimental to selectivity. The pronounced enhancement of AChE inhibition potency and AChE/BChE selectivity was achieved with incorporation of a halogen at the 6-position of homodimeric tacrines. The assay results of 3a-m also provided evidence that the 7-methylene tether tended to be optimal to AChE inhibition potency.
原文英語
頁(從 - 到)2277-2282
頁數6
期刊Journal of Medicinal Chemistry
45
發行號11
DOIs
出版狀態已發佈 - 5月 23 2002

ASJC Scopus subject areas

  • 有機化學

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