A one-pot domino synthesis and discovery of highly functionalized dihydrobenzo[b]thiophenes as AChE inhibitors

作者：Jeyachandran Veerappan; Kumar Raju Ranjith^*; Ali Mohamed Ashraf; Choon Tan Soo

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(7): 2101-2105.

DOI：10.1016/j.bmcl.2013.01.122

• Domino
• Thiophenone
• Malononitrile
• Acetylcholinesterase
• Alzheimer's disease

A library of novel 5-amino-2,7-diaryl-2,3-dihydrobenzo[b]thiophene-4,6-dicarbonitriles have been synthesized regioselectively in good yields through the one-pot domino reactions of 5-aryldihydro-3(2H)-thiophenones, malononitrile and aromatic aldehydes in the presence of morpholine. This transformation presumably involves Knoevenagel condensation-Michael addition-intramolecular Thorpe-Ziegler cyclization-Tautomerization-Elimination sequence of reactions. These compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity and 5-amino-2,7-bis(4-methoxyphenyl)-2,3-dihydrobenzo[b]thiophene-4,6-dicarbonitrile was found to be the most potent against AChE with IC50 4.16 mu mol/L.

• 出版日期2013-4-1