Organocatalyzed Novel Synthetic Methodology for Highly Functionalized Piperidines as Potent α‐Glucosidase Inhibitors. Issue 9 (4th August 2016)

• Record Type: Journal Article
• Authors: Farooq, Ariba; Shahazadi, Lubna; Bajda, Marek; Ullah, Nisar; Rauf, Abdul; Shahzad, Sohail Anjum; Khan, Ather Farooq; Ashraf, Muhammad; Yar, Muhammad
• Is Part Of: Archiv der Pharmazie. Volume 349:Issue 9(2016)
• Page Start: 724
• Page End: 732
• Publication Date: 2016-08-04
• Subjects: 2, 6‐Substituted piperidines -- α‐Glucosidase -- Molecular modeling -- N‐acetyl glycine -- Organocatalysis; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201600045
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract : An efficient atom‐economic one‐pot synthesis of highly functionalized piperidines was achieved by catalytic multicomponent reaction. A wide range of heterogeneous and homogenous catalysts were explored; however, promising results were achieved when a β‐keto‐ester was reacted with selected aromatic aldehydes and anilines by using N ‐acetyl glycine (NAG) as catalyst. The implication of this methodology is straightforward since the products were precipitated out from the reaction solution, eliminating the need of column chromatography purifications. The synthesized piperidines were screened against α‐glucosidase inhibition, which revealed that these compounds were very active inhibitors, and some of the compounds showed even better inhibition than the reference compound, at low micromolar concentrations. In silico molecular modeling was also performed to investigate the binding modes of the compounds into the active sites of the target protein. Abstract : A simple but highly effective novel methodology for the synthesis of functionalized piperidines was developed. The synthesized compounds are α‐glucosidase inhibitors active at low micromolar concentrations. In silico molecular modeling was performed to investigate the potential binding modes of the compounds into the active sites of the target protein.