Fluorinated heterocycles are a major component of the field of modern medicinal chemistry due to the widespread presence of heterocyclic ring structures in naturally occurring biological molecules. The effect of the presence of heterocyclic moieties on chemical properties such as intermolecular interactions and solubility can be used to impart synthetic molecules with useful drug-like characteristics. Heterocyclic compounds are susceptible to fluorine substitution, which can be used to modify the physicochemical properties of synthetic drugs, often improving its biological activity. Pyridazines are aromatic six-membered rings with a chemical formula (CH)4N2, where the nitrogen are in adjacent positions. Pyridazines can improve the biological activities of drug molecules by increasing their solubility in water, and the dipole moment of pyridazines creates a high capacity for complexing with target molecules. Our method incorporates the route reported in “Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro” by Bhambra et al. A library of novel fluorinated pyridazines were synthesized by SNAr reaction of 5,6-fused ring pyridazines with a variety of aryl substituents at the 1- and 4-positions with pentafluoropyridine. The target products were characterized by IR, 1H NMR, 13C NMR, High Resolution Mass Spectrometry, and X-Ray Crystallography. Computational studies were performed on the phenyl case, including the calculation of an optimized structure using PBPPBE with a cc-pVTZ basis.

Synthesis, characterization, and computational studies of fluorinated pyridazines for biological applications

ACS Spring 2022

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