Synthesis of Novel Tacrine Analogs as Acetylcholinesterase Inhibitors

In this work, a wide range of novel pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolin-5-amines were synthesized as tacrine analogs. At first, reaction of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, aromatic aldehydes, and malononitrile gave 6-amino-4-aryl-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles. Then, reaction of the latter compounds with cyclohexanone led to the formation of the title compounds. Also, they were evaluated for their in vitro acetylcholinesterase and butyrylcholinesterase inhibitory activities. Interestingly, most of them showed good inhibitory activity comparing with rivastigmine as the reference drug.