Abstract
The one-pot three-component reaction of 3-methyl-1-phenyl-1,6,7,8-tetrahydro-5H-pyrazolo[3,4-b]quinolin-5-one, aromatic aldehydes, and malononitrile in the presence of piperidine in ethanol has been carried out. The reaction proceeded through domino Knoevenagel condensation - Michael addition - O-cyclization sequence of reactions in a single transformation affording structurally intriguing novel pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles in excellent yields in short reaction time. The high-throughput AChE inhibition studies of these pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles disclosed one compound with maximum potency with an IC
50
value of 2.6 µM/L. The structure-activity relationship revealed that the pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles bearing alkyl or alkoxy substituted phenyl ring at C-4 exhibited more potency than the compounds with halogen-substituted phenyl ring.
The one-pot three-component domino synthesis of novel pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles has been achieved. The high-throughput AChE inhibition studies of these heterocycles disclosed one compound with maximum potency with an IC
50
value of 2.6 µM/L.