Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,b afforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria Staphylococcus aureus, Bacillus cereus and Klebsiella pneumonia and fungi Aspergillus flavus and Aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1 H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.
A new series of quinoline derivatives 5–12 were efficiently synthesized via one-pot multicomponent reaction (MCR) of resorcinol, aromatic aldehydes, β-ketoesters, and aliphatic/aromatic amines under solvent-free conditions. All products were obtained in excellent yields, pure at low-cost processing, and short time. The structures of all compounds were characterized by means of spectral and elemental analyses. In addition, all the synthesized compounds 5–12 were in vitro screened for their antioxidant and antibacterial activity. Moreover, in silico molecular docking studies of the new quinoline derivatives with the target enzymes, human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, were achieved to endorse their binding affinities and to understand ligand–enzyme possible intermolecular interactions. Compound 9 displayed promising antioxidant and antibacterial activity, as well as it was found to have the highest negative binding energy of -9.1 and -9.3 kcal/mol for human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively. Further, it complied with the Lipinski’s rule of five, Veber, and Ghose. Therefore, the quinoline analogue 9 could be promising chemical scaffold for the development of future drug candidates as antioxidant and antibacterial agents.
Compounds 6a and 6b (with pyrimidine moiety, amide linkage, and phenolic substrate) might be potent bacterial flavohemoglobin (flavoHB) inhibitors and they could set a promising starting point for future design of antibacterial agents.
A b d el H aleem M ostafa HusseinC hem istry D ep artm en t, Faculty o f Science, A l-A zh ar U niversity, A ssiu t 71524, Egypt Z. N aturforsch. 53b, 4 8 8 -4 9 4 (1998); received O ctob er 27, 1997 l,2,4-T riazolo[l,5-a]p yrid in es, l,2,4-T riazolo[l,5-a]isoq u in olin es C yan o acid hydrazide 1 was con d en sed with cycloh exan on e in refluxing eth an olic piperidine to yield the hydrazone 4. C om pound 4 reacts with arylidines 5 a -i to yield the 1,2,4triazolo[l,5-a]p yrid in es 7 a -i. C om pound 4 also reacts w ith m ixtures o f aliphatic aldehyd es and different active m eth ylen e reagents to yield l,2.4 -tria zo lo [l,5 -a ]p y rid in es 8 a -d . Sim ilarly reaction o f 4 with arylazom alononitrile to yield the triazolop yrid in es lO a-d. R eaction o f 4 with arom atic ald eh yd es gives 12a-e. C om pound 8a reacts w ith elem en tal sulfur to yield the th ien o-l,2,4-triazolop yrid in e 13. This underw ent cycloadd ition w ith acrylonitrile, a»-nitrostyrene. chalcon e, N -p henylm alem ide, dim eth ylacetylen ed icarb oxylate and tetracyanoethylen e yield in g the isoq u in olin es 15-18. A ll new com poun ds have b een characterized by their IR , 'H N M R and m ass spectra.
Condensation of 3‐oxobutanamide derivative 1 with DMF‐DMA afforded the thiazolopyrimidines 4, pyridine derivative 7 and naphthyridines 12 depending on the different reaction conditions. Condensation of 1 with triethylorthoformate afforded ethoxymethylene derivative 3. The ethoxymethylenes 3 reacted with different nucleophilic reagents to yield 14, 15, 20 and 23–25 respectively. Also, it reacted with malononitrile and ethyl cyanoacetate to give pyridine derivatives 28 a,b. Finally, the ethoxymethylenes 3 reacted with β‐naphthol to yield the benzoquinoline derivative 34.
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