We describe herein the development of novel huperzine A-tacrine hybrids characterized by 3-methylbicyclo[3.3.1]non-3-ene scaffolds. These compounds were specifically designed to establish tight interactions, through different binding modes, with the midgorge recognition sites of human acetylcholinesterase (hAChE: Y72, D74) and human butyrylcholinesterase (hBuChE: N68, D70) and their catalytic or peripheral sites. Compounds 5a-c show a markedly improved biological profile relative to tacrine and huperzine A.
Discovery of Huperzine A-Tacrine Hybrids as Potent Inhibitors of Human Cholinesterases Targeting Their Midgorge Recognition Sites / Gemma, S.; Gabellieri, E.; Huleatt, P.; Fattorusso, Caterina; Borriello, M.; Catalanotti, Bruno; Butini, S.; DE ANGELIS, M.; Novellino, Ettore; Nacci, V.; Belinskaya, T.; Saxena, A.; Campiani, G.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 49:(2006), pp. 3421-3425. [10.1021/jm060257t]
Discovery of Huperzine A-Tacrine Hybrids as Potent Inhibitors of Human Cholinesterases Targeting Their Midgorge Recognition Sites
FATTORUSSO, CATERINA;CATALANOTTI, BRUNO;NOVELLINO, ETTORE;
2006
Abstract
We describe herein the development of novel huperzine A-tacrine hybrids characterized by 3-methylbicyclo[3.3.1]non-3-ene scaffolds. These compounds were specifically designed to establish tight interactions, through different binding modes, with the midgorge recognition sites of human acetylcholinesterase (hAChE: Y72, D74) and human butyrylcholinesterase (hBuChE: N68, D70) and their catalytic or peripheral sites. Compounds 5a-c show a markedly improved biological profile relative to tacrine and huperzine A.| File | Dimensione | Formato | |
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