Pyrano[2,3-f]pyrazolo[3,4-b]quinoline-3-carbonitriles: A three-component synthesis and AChE inhibitory studies

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 IC₅₀ 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.

Graphical Abstract

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 IC₅₀ value of 2.6 µM/L.

Keywords:

• Acetylcholine
• AChE inhibition
• Alzheimer’s Disease
• dementia
• domino reaction
• pyrano[2,3-f]pyrazolo[3,4-b]quinoline

Additional information

Funding

The authors would like to thank Department of Science and Technology, New Delhi, for funds under IRHPA, FIST and PURSE programs. The project was supported by Researchers Supporting Project number RSP-2020/231, King Saud University, Riyadh, Saudi Arabia.