Design and Synthesis of 2-Pyridone Based Flexible Dimers and Their Conformational Study through X-ray Diffraction and Density Functional Theory: Perspective of Cyclooxygenase-2 Inhibition

Abstract

This paper describes the results of X-ray crystallography of 4-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (1) and its propylene bridged dimers 2 and 3. Influence of inter-and intramolecular interactions on the conformation of propylene linker have been studied through single crystal X-ray crystallography and density functional theory studies. Hirshfeld surface analysis has been employed for the study of intermolecular interactions. However, differential scanning calorimetry analysis of compounds 2 and 3, and thermogravimetric analysis of compound 3 has been performed to determine the thermal stability. Along with molecular packing and thermal analysis, molecular docking has also been performed in the catalytic site of cyclooxygenase-2 to identify the potential anti-inflammatory activity of dimer 2 and 3. The above results suggest that the supramolecular aggregate structures which are formed in solution are of lowest energy. However, cyclooxygenase-2 active site prefers the higher energy conformers.

Quantitative Analysis of Intermolecular Interactions in 3‐Cyano‐2‐Pyridones: Evaluation through Single Crystal X‐ray Diffraction and Density Functional Theory

“…The compounds, 4,6‐dimethyl‐2‐oxo‐1,2‐dihydropyridine‐3‐carbonitrile ( 1) , 6‐methyl‐2‐oxo‐4‐phenyl‐1,2‐dihydropyridine‐3‐carbonitrile ( 2) and 4‐methyl‐2‐oxo‐6‐phenyl‐1,2‐dihydropyridine‐3‐carbonitrile ( 3) were synthesised by the known literature methods . However, their methyl derivatives were synthesised by reacting the 2‐pyridones and methyl iodide in equimolar ratio in presence of K 2 CO 3 /DMF at room temperature (Scheme ).…”

“…In the present work, we synthesised 4,6‐disubstituted‐3‐cyano‐2‐pyridones (i. e. 1, 2 and 3 ) and their N‐methyl (i. e. 1 a , 2 a and 3 a ) and O‐methyl (i. e. 1 b , 2 b and 3 b ) derivatives (Scheme ). Subsequently, crystallization of all the molecules was attempted, but compounds 1 , 2 b and 3 b have not been crystallised so far.…”

Multicomponent Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Molecular Docking of 4H‐Pyrans

“…These interactions, including C-H…N, CÀ H…O, CÀ H…π, and π…π, etc., are fundamental cohesive and adhesive forces in the supramolecular self-assembly of molecules. [5,6] Although weak interactions are weaker than hydrogen, ionic, and coordination bonds, they play a crucial role in non-charged and nonpolar compounds and amino acid residues. [7] These strong and weak interactions play a significant role in forming higher-order structures of complex biopolymers like proteins and supramolecular assembly.…”

One-Pot Synthesis of N-Alkylated 2-Pyridone Derivatives under Microwave Irradiation

“…The pyridone derivatives are heterocyclic compounds with vital substructures of many naturally compounds [2] and medicines having a wide range of biological applications, such as antimalarial, antiasthma, vasodilatory, antiepilepsy, antimicrobial, antidiabetic, antiviral, and antioxidant activity, etc. [3]. Over the past decades, much attention has been focused on the synthesis of N-substituted pyridines [4].…”