Diaryl-oxiran-2-yl methanones ( 2 ) were prepared and reacted with thiourea to give 2-thioxo-tetrahydro-pyrimidine-5(2H)-ones ( 3 ).The latter compounds reacted with bromoacetic acid to afford the title compounds ( 4 ). Also some new derivatives were prepared from the reaction of compounds ( 3 ) and ( 4 ) with different reagents. Compounds ( 3 ) were glycosidated with 2,3,4,6-tetra-O-acetyl-α -D-glucopyranosylbromide (α -ABG) to afford the corresponding nucleosides.
Combination of arylidene hydrazinyl moiety with pyrido[2,3-d]pyrimidin-4-one skeleton in compounds 7‒26 results in the output of unprecedented anti-microbial agents. Arylidene hydrazinyl based on Pyrido[2,3-d]pyrimidin-4-one analoges 7‒26 prepared by the treatment of [2,3-d]pyrimidin-4-ones 6a,b with various aromatic aldehydes. The antimicrobial action for recently synthesized compounds was considered towards gram positive bacterial species (Staphylococcus aurous ATCC- 47077; Bacillus cereus ATCC-12228), gram negative bacterial species (Escherichia coli ATCC-25922; Salmonella typhi ATCC-15566) and Candida albicans ATCC-10231 as fungal strains. The antimicrobial action expanded by expanding the electron donating group in position 2 and 5 for Pyrido[2,3-d]pyrimidin-4-one core. Derivatives 13, 14, 15, 16 and 12; individually appeared hopeful anti-microbial action towards all strains utilized with inhibition zone higher than that of standard reference drug with lowest MIC.
17 April 2023 in International Journal of Biological Macromolecules
4-(2-(4-Halophenyl)hydrazinyl)-6-phenylpyridazin-3(2H)-ones 1a,b were prepared and treated with phosphorus oxychloride, phosphorus pentasulphide and ethyl chloroformate to give the corresponding chloropyridazine, pyridazinethione, oxazolopyridazine derivatives 2–4, respectively. Compound 2 reacted with hydrazine hydrate to afford hydrazinylpyridazine 7. The reaction of 4-(2-(4-chlorophenyl)hydrazinyl)-3-hydrazinyl-6-phenylpyridazine (7) with acetic anhydride, p-chlorobenzaldehyde and carbon disulphide gave the corresponding pyridazinotriazine derivatives 8–10. On the other hand, 5-(4-chlorophenylamino)-7-(3,5-dimethoxybenzylidene)-3-phenyl-5H-pyridazino[3,4-b][1,4]thiazin-6(7H)-one (11) was prepared directly from the reaction of compound 3 with chloroacetic acid in presence of p-chlorobenzaldehyde. Compound 11 reacted with nitrogen nucleophiles (hydroxylamine hydrochloride, hydrazine hydrate) and active methylene group-containing reagents (malononitrile, ethyl cyanoacetate) to afford the corresponding fused compounds 12–15, respectively. Pharmacological screening for antiviral activity against hepatitis A virus (HAV) was performed for the new compounds. 4-(4-Chlorophenylamino)-6-phenyl-1,2-dihydropyridazino[4,3-e][1,2,4]triazine-3(4H)-thione (10) showed the highest effect against HAV.
A series of novel pyridine and fused pyridine derivatives have been prepared starting from 6-(3,4-dimethylphenyl)-2-hydrazinyl-4-(thiophen-2-yl)-pyridine-3-carbonitrile 1 which on treatment with appropriate formic acid, acetic acid/acetic anhydride, benzoyl chloride and/or carbon disulfide afforded the corresponding triazolopyridine derivatives 2–5. Also, treatment of hydrazide 1 with diethyloxalate, chloroacetyl chloride, chloroacetic acid and/or 1,2-dichloroethane yielded the corresponding pyridotriazine derivatives 7–10. Further transformation of compound 1 with a different active methylene group, namely acetyl acetone, diethylmalonate, ethyl cyanoacetate, ethyl benzoylacetate and/or ethyl acetoacetate, produced the pyridine–pyrazole hybrid derivatives 11–15. These newly synthesized compounds (1–15) were subjected to in silico molecular docking screenings towards GlcN-6-P synthase as the target protein. The results revealed moderate to good binding energies of the ligands on the target protein. All the newly prepared products exhibited antimicrobial and antioxidant activity.