Synthesis and characterization of new 4-aryl-2-(2-oxopropoxy)-6-(2,5-dichlorothiophene)nicotinonitrile and their furo[2,3-b]pyridine derivatives: Assessment of antioxidant and biological activity

Abstract

A new series of furo[2,3-b]pyridine derivatives bearing aryl substituents were synthesized in two steps, where, the cyano-(2H)-pyridones (1a-l) were converted to the corresponding nicotinonitriles (2a-l), followed by the Thorpe-Ziegler ring cyclization to the furo[2,3-b]pyridine derivatives (3a-l). All new compounds were characterized by 1D-NMR experiments (1H and 13C) and 2D-NMR experiments (COSY, HMBC and HSQC), as well as ESI-MS and HR-ESI-MS data. The new compounds were screened for their antioxidant activities by 2,2-diphenyl-1-picryl-hydrazylhydrate (DPPH) free radical assay. The highest radical scavenging effect was observed for nicotinonitriles 2d, 2h and 2l and furo[2,3-b]pyridines 3b, 3f and 3j by methanolic solvent at 4.0 mg/mL concentration. Remarkably, all nicotinonitriles and furo[2,3-b]pyridine exhibited a significant radical scavenging activity after 24 and 48 hours compared with 0.5 hour.

Synthesis of 1-Amino-3-oxo-2,7-naphthyridines via Smiles Rearrangement: A New Approach in the Field of Chemistry of Heterocyclic Compounds

“…Furthermore, it is well known that fused derivatives of furo[2,3- b ]pyridine show high biological activity [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Along this line we have previously synthesized several condensed furo[2,3- b ]pyridines based on the cyclopenta[ c ]pyridines, 5,6,7,8-tetrahydroisoquinolines and pyrano[3,4- c ]pyridines, obtaining compounds with neurotropic [ 25 , 26 ], antimicrobial [ 27 ], antitumor [ 28 ] and potent antiviral [ 29 ] activities.…”

The Synthesis, Characterization, Cytotoxic Activity Assessment and Structure–Activity Relationship of 4-Aryl-6-(2,5-dichlorothiophen-3-yl)-2-methoxypyridine-3-carbonitriles

“…Furthermore, they are important precursors for synthetic manipulations and have been commonly used as precursors and key intermediates in organic synthesis [12,13]. In recent years, we reported the synthesis of different pyridine derivatives bearing carbonitrile and 2,5-dichlorothiophene substituents [14,15,16,17,18,19]. In continuation of our ongoing work, herein, we present the synthesis and characterization of new pyridine-3-carbonitrile derivatives (Scheme 1).…”