Discovery of huperzine A-tacrine hybrids as potent inhibitors of human cholinesterases targeting their midgorge recognition sites

作者：Gemma Sandra; Gabellieri Emanuele; Huleatt Paul; Fattorusso Caterina; Borriello Marianna; Catalanotti Bruno; Butini Stefania; De Angelis Meri; Novellino Ettore; Nacci Vito; Belinskaya Tatyana; Saxena Ashima; Campiani Giuseppe^*

来源：Journal of Medicinal Chemistry, 2006, 49(11): 3421-3425.

DOI：10.1021/jm060257t

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.

• 出版日期2006-6-1