Homodimeric tacrine congeners as acetylcholinesterase inhibitors

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

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2277-2282
Number of pages6
JournalJournal of Medicinal Chemistry
Volume45
Issue number11
DOIs
Publication statusPublished - May 23 2002

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Tacrine
Cholinesterase Inhibitors
Butyrylcholinesterase
Halogens
Rats
Assays
Derivatives

ASJC Scopus subject areas

  • Organic Chemistry

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Homodimeric tacrine congeners as acetylcholinesterase inhibitors. / Hu, Ming Kuan; Wu, Li Ju; Hsiao, George; Yen, Mao Hsiung.

In: Journal of Medicinal Chemistry, Vol. 45, No. 11, 23.05.2002, p. 2277-2282.

Research output: Contribution to journalArticle

Hu, Ming Kuan ; Wu, Li Ju ; Hsiao, George ; Yen, Mao Hsiung. / Homodimeric tacrine congeners as acetylcholinesterase inhibitors. In: Journal of Medicinal Chemistry. 2002 ; Vol. 45, No. 11. pp. 2277-2282.
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