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Due to the recent emergence of drug-resistance of antidiabetic drugs and the increase in the number of diabetes cases around the world, the search for and discovery of more effective a-amylase inhibitors is of great interest. In the present study, a new series of eighteen ortho-carboxamidostilbene derivatives were synthesized via Heck coupling reaction. The structures of the synthesized compounds were identified by various spectroscopic techniques, including HREIMS, FTIR and 1D-NMR. In addition, the compounds were evaluated in vitro for their potential a-amylase inhibitory potency using acarbose as the reference drug. Compounds 5e, 5f and 6e showed remarkably moderate to good inhibitory activity with IC50 values ranging from 13.3 - 28.2 µM. These compounds showed potent IC50 values compared to the reference drug acarbose (IC50 = 30.2 ± 0.1 µM). The in silico molecular docking studies revealed the binding interactions of the most active ortho-carboxamidostilbene derivatives (5e and 6e) with binding energies of -8.7 ± 0.0 and -8.6 ± 0.2 kcal/mol, respectively. Based on the structure-activity relationship (SAR) analysis, it was established that variations in the inhibitory activities of a-amylase enzymes were attributed to distinct types of substituents at the amide group of the aryl ring A along with the number and position of methoxy groups attached to the aryl ring B. These findings highlight the a-amylase inhibitory properties of orthocarboxamidostilbene containing cyclohexane and phenyl moieties, serving as potential lead compounds in antidiabetic drug development for the treatment of type II diabetes mellitus. [ABSTRACT FROM AUTHOR]

Syntheses of substituted pyridines and fluorinated compounds, which are often pharmaceutical targets, are important objectives in organic chemistry. Herein, we found that decarboxylative fluorination of lithium 2-pyridylacetates occur under catalyst-free conditions. The phenomenon can be applied to one-pot transformation of substituted methyl 2-pyridylacetate to 2-(fluoroalkyl)pyridine by decarboxylative fluorination of the intermediate lithium 2-pyridylacetate. This method was also applied to the syntheses of 2-(difluoroalkyl)pyridines., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)