Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids dehydroevodiamine and rutaecarpine

Derived from the structures of the alkaloids rutaecarpine and dehydroevodiamine (DHED), and the long-known acetylcholinesterase (AChE) inhibitor tacrine, respectively, novel compounds were synthesised, including: 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (12), (8Z)-5,6-dihydro-8H-isoquino[1,2-b]quinazolin-8-imine (13), 5,8-dihydro-6H-isoquino[1,2-b]quinazoline (15a), 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (16), 5,7,8,13-tetrahydroindolo [2′,3′:3,4]pyrido[2,1-b]quinazoline (17), and N-(2-phenylethyl)-N-[(12Z)-7,8,9,10-tetrahydroazepino [2,1-b]quinazolin-12(6H)-ylidene]amine (20), respectively. In a first step to evaluate their possible applicability for antiamnesic therapy, the inhibition of AChE and butyrylcholinesterase (BChE) were determined: compounds 13, 15a, 17, and 20 are moderate or strong inhibitors of ChE, the latter two compounds show a 10-fold higher affinity to BChE. Compound 12 is a moderate inhibitor of AChE showing selectivity towards this enzyme.