Synthesis and antimicrobial activity of novel pyrido[2,3-d]pyrimidin-4(1H)-ones, and 2-pyrazoline derivatives

Abstract

The synthesis of chalcone 1 allowed the production of a novel group of compounds by linking indole with thiophene moieties. The new series of substituted pyridines 2-8, 2-pyrazolines 9-14, and azepines 15, 16 were synthesized using chalcone 1 as a crucial intermediate. 2-Aminopyridines 2, 3, and 4 were produced by reacting compound 1 with cyanoacetamide, ethyl cyanoacetate, and malononitrile, repectively. The α,βunsaturated ketone 1 underwent conversion to 2-thioxodihydropyridopyrimidinone 5 and 2-hydrazinyl pyridopyrimidinone 6. These compounds served as the initial substrate for the synthesis of compounds 7 and 8. 1-Thiocarbamoyl-2-pyrazoline 9 was synthesized by the cycloaddition reaction between thiosemicarbazide and chalcone. 1-(4-oxo-5H-thiazolyl)-2-pyrazoline 10 and 1-(4-phenylthiazolyl)-2-pyrazoline 11 were synthesized by treating thiocarbamoyl derivative 9 with chloroacetic acid or phenacyl bromide. Condensation of thiazolyl pyrazoline 10 with aromatic aldehydes yielded the arylidenes 12-14. The α,β-unsaturated ketone 1 underwent a reaction with bifunctional agents such as o-phenylenediamine or o-aminophenol, resulting in the formatipn of azepines 15 and 16. The novel compounds were structurally determined with spectral data including FTIR, ¹H NMR, ¹³C NMR, and MS spectroscopy as well as elemental analysis. In addition, the new substances were tested for antibacterial activity versus an array of Gram positive and Gram-negative bacteria, as well as four fungal species. Our findings revealed that 2-pyrazolines 9-14 had remarkable effects when compared to the other compounds.